Hermansky-Pudlak Syndrome (HPS) Simple Guide + Podcast

Everything to know about HPS, from the experts.

Podcast

Author and Contributing Experts to this Guide include:

Lauren Giannetti Sferrazza Certified and Licensed Genetic Counselor LinkedIn
Donna Appell Executive Director and Founder of the Hermansky-Pudlak Syndrome Network LinkedIn
Heather Kirkwood COO and Chief Communications Officer at the Hermansky-Pudlak Syndrome Network LinkedIn
Olivia Maher Genetic Counseling Intern/Student LinkedIn

Interviewees

Lauren Giannetti Sferrazza is a certified genetic counselor who works at Myriad Genetics as a Regional Medical Specialist in Oncology. Lauren completed her master's thesis about Hermansky-Pudlak Syndrome at Long Island University which was published as an abstract in the Journal of Genetic Counseling in 2014.

Donna Appell is a registered nurse who is the Founder and Executive Director of the Hermansky-Pudlak Syndrome Network, and the mother of a daughter with HPS.

Heather Kirkwood was diagnosed with HPS in her 20’s and is an integral part of the Hermansky-Pudlak Syndrome Network as their Chief Operations Officer and Director of Communications.

What is Hermansky-Pudlak Syndrome (HPS)?

Hermansky-Pudlak syndrome (HPS) is a rare hereditary disorder characterized by a condition called oculocutaneous albinism. This causes abnormally light pigmentation of the skin, hair, and eyes 1.

In addition, people with HPS have a higher than average risk of skin damage and skin cancers caused by long-term sun exposure 2.

Because oculocutaneous albinism reduces pigmentation of the iris, the colored part of the eye, and the retina, the light-sensitive tissue at the back of the eye, HPS is also associated with reduced vision, nystagmus, or rapid and involuntary eye movements, and photophobia, or increased sensitivity to light 3.

Other symptoms of HPS include blood platelet dysfunction with prolonged bleeding that can lead to easy bruising. In some cases, HPS causes pulmonary, or lung, fibrosis which can produce scar tissue to form on the lungs.

Pulmonary fibrosis typically causes symptoms in the early thirties and can lead to death within a decade 4. Additionally, some individuals with HPS may also experience granulomatous colitis, or inflammation of the large intestine, kidney failure, and ceroid lipofuscin, or an abnormal storage of a fatty-like substance in various tissues of the body 5.

HPS is also sometimes referred to as albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells, or delta storage pool disease 6.

There are at least nine different types of HPS, distinguished by their signs and symptoms and underlying genetic cause 7:

  • Types 1 and 4 are the most severe forms of the disorder.
  • Types 1, 2, and 4 are the only types associated with pulmonary fibrosis.
  • Types 3, 5, or 6 have the mildest symptoms.
  • Little is known about the signs, symptoms, and severity of types 7, 8, and 9.

What Causes Hermansky-Pudlak Syndrome?

HPS is a rare genetic disorder. At least nine genes are associated with this condition.

These genes provide instructions for making proteins that make four protein complexes that play a role in the formation and trafficking of a small group of cell structures called lysosome-related organelles (LROs) 8.

Lysosomes digest and recycle materials throughout our bodies, and LROs are similar, but LROs perform specialized functions and are found only in certain cell types 9.

LROs have been identified in pigment-producing cells (melanocytes), blood-clotting cells (platelets), and lung cells. When a gene associated with HPS has a pathogenic variant, or a genetic change that does not allow that gene to function properly, LROs are subsequently unable to form or function properly 10.

Changes in genes that impact LROs cause changes that are seen throughout the body since LROs are needed in so many different cell types. For example, people with HPS have oculocutaneous albinism because the LROs in the melanocytes cannot produce and distribute the substance that gives skin, hair, and eyes their color (melanin) 11.

The absence of LROs in platelets causes bleeding problems, and affects the ability of platelets to stick together and form a blood clot 12.

When changes occur in some of the genes that cause HPS, it can also affect the normal functioning of LROs in lung cells, leading to pulmonary fibrosis 13.

The identified mutated genes that cause HPS include 14:

  • AP3B1
  • AP3D1
  • BLOC1S3
  • BLOC1S6
  • DTNBP1
  • HPS1
  • HPS3
  • HPS4
  • HPS5
  • HPS6

Mutations in the HPS1 gene cause approximately 75% of the HPS cases from Puerto Rico, which is an area that is impacted by HPS at a much higher rate due to a Founder’s Effect 15. About 45% of affected individuals from other populations have mutations in the HPS1 gene 16.

Mutations in the HPS3 gene are found in about 25% of affected people from Puerto Rico and in approximately 20% of affected individuals from other areas 17.

The other genes associated with HPS each account for a small percentage of cases of this condition 18.

In many cases, the genetic cause of HPS can’t be identified 19.

HPS is inherited in an autosomal recessive pattern 20. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes-- these chromosomes do not determine our sex but provide our body with instructions on how to complete all of our other functions, like producing LROs or maintaining lung function.

Recessive means that both copies of the responsible gene must be altered to have the condition.

Although the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, they typically do not have signs or symptoms of the condition-- these individuals are known as carriers 21.

When two carriers of an autosomal recessive condition have children, there is a 25% chance with each new pregnancy to have a child with the condition 22.

“With autosomal recessive inheritance, we have two copies of every gene. One from mom and one from dad. And when we're looking at these genes associated with Hermansky-Pudlak Syndrome, let's say the HPS1 gene, we're going to get one copy from mom and one copy from dad.

“If for some reason, both of those copies have the mutation, something in the genes is going to make it nonfunctional and when you inherit both copies of those, it doesn't allow you to have any functioning HPS1 gene,” said Lauren Giannetti Sferrazza, a certified genetic counselor who works at Myriad Genetics as a Regional Medical Specialist in Oncology.

Sferrazza completed her master's thesis about Hermansky-Pudlak Syndrome at Long Island University which was published as an abstract in the Journal of Genetic Counseling in 2014.

“The function of that gene is completely knocked out. You don't have a backup copy. So you manifest symptoms of HPS.

“As for the risks to other siblings or other people in the family, this is not something if you're a carrier you'll know, unless you do genetic testing carrier screening or unless that there's a family history,” she added.

This puts a premium on family planning, awareness, and the need for genetic counseling to fully understand the risks.

“When you’re a carrier, each new pregnancy, each new child is a new risk. Just because parents don’t have a child who has HPS, it doesn't mean that they wouldn't have another child with HPS.

“With every single pregnancy, if you're both carriers, would be a 25% chance, which depending on what you're thinking about, it doesn't seem that high, but it's still a good chance. And it's still something that is good to know about in advance.

There's a lot of people that didn't know they were carriers or didn't know this condition was in the family until they had a child that was affected with it,” said Sferrazza.

Signs & Symptoms of Hermansky-Pudlak Syndrome

There are several signs and symptoms of HPS. These will vary by the type and severity of the condition from person to person.

“Not everybody with HPS will present exactly the same. There are a lot of different subtypes and they just keep getting discovered as well. I know one was just discovered in the past few months. But, in general, every single person with Hermansky-Pudlak Syndrome, no matter the subtype, will have some sort of ocular albinism or ocular findings,” said Sferrazza.

“One of the things that you might see is nystagmus. That is when you see somebody's eyes moving rapidly from side to side. Albinism is also a key feature, but not every person with Hermansky-Pudlak Syndrome actually has albinism. Albinism, meaning that they have very, very white skin, they have white hair, they usually will have very light-colored eyes.

“Obviously, because of the albinism, a person with HPS can't be in prolonged sun exposure, but not everybody with Hermansky-Pudlak Syndrome has albinism. And that's why it's misdiagnosed a lot.

“The other very key feature of Hermansky-Pudlak Syndrome is the platelet defect that these individuals have. And unfortunately, a lot of times this is also misdiagnosed as a clotting problem. It's not that they don't have the proteins for clotting or there's a mutation in one of the clotting factors, it's that their platelets are missing what we call delta granules… because they're missing these delta granules in their platelets, they will have really high risk of bleeding and nosebleeds.” she added.

HPS is a condition that impacts many different parts of the body. There are many different ocular manifestations of HPS, or symptoms that impact the eye.

Oculocutaneous albinism, or the absence of color in the eye, is often seen in individuals with HPS as is nystagmus, or involuntary, rapid eye movements. Individuals with HPS also may experience a significant reduction in visual acuity as well as amblyopia, or what is colloquially known as lazy eye, strabismus, or cross-eyed, and cataracts 23.

HPS also impacts the skin, so individuals with HPS may experience partial albinism, which is the partial absence of skin coloring with lighter hair and eyes as compared to other family members.

Albinism can cause photophobia, or sensitivity to light, which can subsequently lead to a higher risk of skin cancer and pachydermia, which is when the skin thickens and becomes more coarse and rough after prolonged, repeated sun exposure 24.

Pulmonary fibrosis, or scarring of the lungs that impacts lung function, is another symptom that is seen in some types of HPS. Individuals with HPS may also experience other complications of their internal organs, like kidney insufficiency and heart disease.

There are often gastrointestinal complications as well, such as granulomatous colitis, or inflammation of the colon, malabsorption, or poor absorption of nutrients from food, and rectal bleeding 25.

Platelets are also impacted by HPS, and can lead to neutropenia, or depleted blood neutrophil count. Neutrophils are an important part of our immune system, so a low number of these can cause individuals with HPS to be immunocompromised 26.

Bleeding diathesis (prolonged bleeding), due to abnormal platelets, can result in variable bruising, nose bleeds, bleeding of the gums, postpartum hemorrhage, and rectal bleeding. Prolonged bleeding may be present after tooth extraction, circumcision, and other surgeries 27.

Also, menstrual cycles may be heavy and irregular 28.

Why do People with Hermansky-Pudlak Syndrome Bleed Easily?

Sferrazza studied patients with HPS in Puerto Rico, where the incidence of this condition is higher than normal 29.

“When I went to Puerto Rico, I met with a bunch of people. Some had albinism, some didn't, but everybody I met with said that they had some sort of nosebleed that they were having a hard time stopping. When they would go in for dental procedures it was not a good situation. Childbirth was really dangerous for a lot of people.”

Understanding that there is a platelet issue of any kind is critical to wound care-- That is the case with someone who has HPS 30.

“When you're going to the hospital with an emergency, these individuals need platelets. And that's a very, very specific ask. The providers that are treating them need to know that because you don't want to bleed out. Unfortunately, quite a few people have passed away due to these really severe bleeding issues.”

Because the severity of HPS varies, the milder types may just have the ocular features and the platelet issues.

“On the more severe end of the spectrum, albinism would be present. There's also some colitis. So gastrointestinal issues as well.”

What Causes Pulmonary Fibrosis in Hermansky-Pudlak Syndrome?

According to Sferrazza, “On the worst end of the spectrum is pulmonary fibrosis. And this leads to many people needing lung transplants.”

“Quite a few people, unfortunately, have passed away due to the pulmonary fibrosis. Your lungs are supposed to, when you breathe in, expand and contract. And if you have fibrosis, it doesn't allow the lungs to do that. The lungs become really kind of hard and people, unfortunately, are not able to breathe. HPS1 presents this way.”

People with pulmonary fibrosis can receive lung transplants, which can lead to a new lease on life. But getting a transplant can be challenging.

One of the big issues is, “…getting on the transplant list, how long it takes. Some of these individuals are immune-compromised and can be very sick.

And so sometimes lungs become available and then they are not fit health wise to have the lungs implanted. There's a lot of different variability. And I think that's why it's so commonly misdiagnosed,” said Sferrazza.

Potential Complications of Hermansky-Pudlak Syndrome

The main complications arising from HPS are hemorrhagic diathesis, or prolonged bleeding, and pulmonary fibrosis 31.

Issues related to bleeding are especially concerning, because they can happen to anyone who has HPS.

“If somebody gets cut, like if you're a little kid and you fall and you scrape your elbow, usually what do we all think? Okay. You clean it up and you throw a bandage on it. You don't think anything else.

“But people with HPS will continue to bleed through those band aids. What they taught me at the HPS Network was you’ve got to slap on some petroleum jelly, Vaseline. That's got to be in your first aid kit because it creates a barrier. And then you've got to do a very specific pathway to treating that wound, even if it's just a small cut. That's a big difference, a band aid versus using Vaseline and gauze and all of these different things,” said Sferrazza.

Problems with excessive bleeding remain an issue in virtually all parts of a person’s life. Surgeries of any type must be approached cautiously 32. HPS during pregnancy must be monitored closely as well 33.

Even when bleeding does not occur, a simple bump can produce huge bruises 34.

“A lot of times when kids go to school with bruises, they start thinking that there's abuse happening in the home,” added Sferrazza.

Also, with albinism, skin cancer may be more prevalent as well though increased incidence of skin cancer has not been directly linked to HPS 35.

Pulmonary fibrosis is the other major concern because it is fatal over time 36. Most people pass away within 10 years of their first diagnosis 37. The lungs eventually scar up to the point where they no longer function effectively 38. In most cases, the only solution is a lung transplant.

The other complications include eye issues. Most HPS patients need glasses, and many are legally blind 39.

Prevalence and Risk Factors of Hermansky-Pudlak Syndrome

In most populations, HPS is estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. However, Type 1 is more common in Puerto Rico, particularly in the northwestern part of the island where about 1 in 1,800 people are affected.

Type 3 is common in people from central Puerto Rico. Clusters of groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe 40.

“Type one is the most severe form, very likely the most common form. Type three is a more mild form where you would see just the bleeding issues and the eye issues and usually not the pulmonary fibrosis. Those two are very, very common in Puerto Rico. Those are usually found in the northwestern and central parts of Puerto Rico,” said Sferrazza.

“The island effect creates a high degree of carrier frequency of Hermansky-Pudlak Syndrome. This is a recessive condition, autosomal recessive. So, you could be a carrier and obviously not have any symptoms, but the carrier frequency is one in 20, which is more common than cystic fibrosis. And then in general in Puerto Rico, the frequency of Hermansky-Pudlak Syndrome is about one in 60.”

“Maybe this has changed, but the last time I had looked, this was not part of newborn screening in Puerto Rico, which is really disheartening since it is such a common condition and it really does need intervention as early as birth for that individual,” she added.

HPS is also common in the Ashkenazi Jewish population 41.

“Ashkenazi Jewish populations do have quite a few conditions that they are more at risk for. Just like Puerto Rico, kind of that population effect where if you are continuing to have partners within the same population, there's not that genetic diversity. In Puerto Rico, it's an island effect, because people don't necessarily leave the island.”

According to Sferrazza, newborn testing should also extend to possible impacted populations in the United States, such as in New York City where many individuals of Puerto Rican descent have migrated.

Many people are surprised at how comparatively prevalent it is, according to Donna Appell. She is a registered nurse who is the Founder and Executive Director of the Hermansky-Pudlak Syndrome Network, and the mother of a daughter with HPS.

“A lot of people have never heard of it before. But it has the same incidence as cystic fibrosis. And you've heard of that. In the European or Caucasian population, the incidence, the disease is cystic fibrosis. And it's in every other nationality, but it's really prevalent in that one.”

“The same goes with sickle cell [disease] to people of African American and Tay-Sachs for Jewish people. For Puerto Rican people, the rate of incidence is the same, but nobody's heard of HPS. I think what I really like everybody to know is that there's a real big healthcare disparity here.”

“I could really appreciate and use a bunch of soldiers out there to get the word out about Hermansky-Pudlak Syndrome, because we need the outreach. We need people to be aware of it just as they're aware of other diseases that have similar incidence levels,” said Appell.

Diagnosis of Hermansky-Pudlak Syndrome

HPS is diagnosed through a combination of clinical features, laboratory testing, and genetic testing.

Clinical features include wandering eye movement or a lack of visual attention are present, along with skin and hair color that are lighter than other family members (oculocutaneous albinism) 42.

Oculocutaneous albinism is also associated with the following characteristic ocular findings 43:

  • Reduced iris pigment
  • Reduced retinal pigment

Another clinical feature is if prolonged bleeding is present after minor procedures such as circumcision or a tooth extraction 44.

If clinical features are not conclusive, family studies may take place to move closer to a confirmed diagnosis.

Laboratory testing may further confirm a possible diagnosis by conducting a variety of coagulation studies, including 45:

  • Platelet aggregation testing showing impaired secondary aggregation response
  • Prothrombin time, partial thromboplastin time, and platelet counts typically normal
  • Bleeding time generally prolonged
  • Absence of platelet delta granules (dense bodies) on whole mount electron microscopy

When dense bodies, which contain ADP, ATP, serotonin, calcium, and phosphate, release the contents of their granules to attract other platelets, the process initiates the secondary aggregation response. This cannot occur in the absence of the dense bodies.

There are normally four to eight dense bodies per platelet but there are no dense bodies in the platelets of patients with HPS 46.

Genetic testing can include single-gene testing, a multi-gene panel, or comprehensive genomic testing.

Most single-gene testing is done for the HPS1 gene and is generally targeted to people of northwestern Puerto Rican ancestry. Single-gene testing for the HPS3 gene is targeted to people of Ashkenazi Jewish ancestry 47.

Depending on the severity of the clinical symptoms (especially visual acuity), multi-gene testing may be ordered. A multigene panel that includes AP3B1, AP3D1, BLOC1S3, BLOC1S6, DTNBP1, HPS1, HPS3, HPS4, HPS5, HPS6, and other genes of interest.

Other genes may be considered as part of a differential diagnosis possibility 48.

Clinicians will attempt to determine which multigene panel will be best to identify the genetic cause of the condition at an appropriate cost while also limiting identification of mutated variants in genes that do not explain the underlying cause of symptoms.

In some cases, more comprehensive genomic testing including exome sequencing and genome sequencing may be considered. This is due to the large number of genes associated with HPS and this type of testing may provide or indicate a diagnosis that was not previously considered 49.

Clinicians will look for several possible differential diagnoses, based on a variety of symptoms and test results. Some of these similar conditions may include:

  • Albinism. The diagnosis of HPS should be considered in anyone with oculocutaneous albinism or ocular albinism, but it should also be combined with an examination of platelets for absent dense bodies. Oculocutaneous albinism does not automatically mean a patient has HPS. The condition can exist by itself. X-linked ocular albinism is caused by a mutated GPR143 gene, but this is a different condition than HPS 50.

  • Disorders of platelet-dense bodies. Similar disorders can include Chediak-Higashi syndrome (CHS), caused by biallelic mutations in the LYST gene or Griscelli syndrome is also another platelet-dense bodies disorder that may present similar to HPS 51.

Genetic testing is highly recommended in families where parents are known carriers. Carrier testing for at-risk family members is possible if the AP3B1, AP3D1, BLOC1S3, BLOC1S6, DTNBP1, HPS1, HPS3, HPS4, HPS5, or HPS6 pathogenic variants in the family have been identified 52.

Genetic counseling is also recommended so that families can evaluate the level of risk and possibly identify a diagnosis early, leading to more effective treatment. The optimal time for discussing genetic risks are through prenatal testing before pregnancy.

Medical professionals and family may have differing opinions on prenatal testing if it is being considered as a possible determining factor for pregnancy termination instead of early diagnosis 53.

One of the challenges patients face is finding ways to connect the diagnostic pieces to make an accurate assessment.

“For me, what I found was that a lot of providers were seeing these symptoms piecemeal. So they weren't putting it all together. Maybe when they went to the ER, the doctor would say, ‘Oh, you probably have a bleeding issue.’

“But they never did the testing because it's a very specific test for the platelet issues. So, they never looked further into it. They just said, ‘Oh, you've got factor something deficiency. Maybe you have hemophilia."

There's a lot of times people were misdiagnosed, just being told, ‘Oh, you got albinism, that's it.’ But they never went further to say, ‘Oh, you have nystagmus. Oh, you have pulmonary fibrosis. Oh, you have bleeding tendencies,” said Sferrazza.

“We need to do a better job as a healthcare system and as providers to identify these individuals. Just because you are an eye doctor, ophthalmologist or whatever, it doesn't mean that you don't ask about these other organ systems.

“People now have the Internet and the HPS Network has a website. I think now I'm seeing younger kids being diagnosed because maybe they're seeing a geneticist earlier on because parents know, ‘Hey, there's something going on here. I'm going to bring my kid to a geneticist.’ Whereas maybe many years previous, they'd just say, ‘Yeah, you got albinism. It is what it is.’ But bringing them to a specialty clinic has been really helpful,” she added.

Heather Kirkwood’s Diagnostic Journey

Heather Kirkwood was diagnosed with HPS in her 20s. She is an integral part of the Hermansky-Pudlak Syndrome Network as their Chief Operations Officer and Director of Communications. She recently offered several unique insights as someone who has been diagnosed with HPS.

“My brother and I both have HPS, but I wasn't diagnosed until I was 29. A few years before, I had really bad bowel disease in college and ended up having to have an ileostomy. And thank God, there was a hematologist who told [my mother] that her kids might bleed. She decided, if there is anything serious to happen, she needed to get a hematologist involved.

“I was very, very ill and this is before the internet is the way it is now. So the hematologist cancelled his appointments for the day, goes into the medical library, comes back after a day of research with this book and that has one little paragraph. He said, ‘I think if we give you some platelets, you'll be fine.’ That wasn't really a diagnosis or anything, but anyway, thank God.

“I was very lucky because I don't think I would've survived that surgery if he hadn't given those platelets. After that, I was sick of dealing with medicine and medical stuff [since] I was healthy and doing fine. I didn't think much of it. I just kind of went on with my life until I was 29.

“I had a sinus infection, which has nothing to do with HPS, but I couldn't get rid of it. A friend of mine was a nurse. I went to a doctor that she worked with for a second opinion, and on the medical history, I wrote down Hermansky-Pudlak Syndrome. And the doctor, after a week, went to all the stuff for the sinus infection.

“She says, ‘What is this about this Hermansky-Pudlak Syndrome? What is that?’ And I was really embarrassed that I really didn't know.

“I went back to my office and Googled it and started pulling up these papers that said, ‘You[r lungs] usually fail in the third to fourth decade.’ And yada, yada.

“I got upset and called my mom who got upset. So we called my aunt-- the sane person in the family -- she got online and found Donna Appell and called me back at work and said, ‘You need to call this lady.’ I called her immediately, and I was at the NIH three months later where I got an official diagnosis of Hermansky-Pudlak Syndrome.

“There were a couple of bleeding instances over the years. I was worked up for bleeding disorder four times and everything came back normal. But by the grace of God, we never had anything serious happen.

“I tell people the scary part is not having Hermansky-Pudlak Syndrome. It's having it and not knowing it, because you can't treat it.

“I received a single lung transplant about two and a half years ago. That is trading one disease for another, definitely. I mean, I kind of knew that going in, but it's definitely been that way.

“Right now, I'm having some rejection. To treat that, they have really immunosuppressed me. I have to be very careful because everybody's wearing these masks [as a COVID-19 precaution] as if it's a new thing and that's what I do all the time.

“Before the transplant, there are certain milestones in people's lives that are real markers. First, it's getting the diagnosis. And then it's when you start having trouble breathing. Then it's when you have to go on oxygen. And then it's deciding if you want to go for a lung transplant or not, which is a big decision. It requires a lot of planning and fundraising.

“The hardest thing [about] living with the transplant is... the immune suppression and how you have to be so careful. There's all these food rules. For example, you can't have a salad out in public because you can't be sure that the lettuce has been washed thoroughly.

“You know smoothies are like a big deal right now. There are smoothie places everywhere. And we're not supposed to do those because you just don't know if the fruit was washed. When I eat out, I try to eat something that's cooked.

“Also, I think sometimes people don't realize the vision issue because we adjust to it so well. Most people with HPS are legally blind. Not all. Some have vision issues, but they're not legally blind, but most of us are legally blind, but we still see quite a bit. We have quite a bit of functional vision.

It's funny because even people you've lived with your whole life, your parents and such, don't fully appreciate sometimes what you can see and can't see. My brother and I have this sort of inside joke. When we were kids, we'd drive in the car.

We lived in Colorado. And then my mom would go, ‘There's deer. There's a deer. Look, right there. He's right there.’ So we just thought, [and] we would say, ‘We see it.’”

Can Hermansky-Pudlak Syndrome be Cured?

Research is ongoing, but at the present time, there is no cure for Hermansky-Pudlak syndrome 54.

Treatment and Care Options for Hermansky-Pudlak Syndrome

Treatment for HPS centers on preventing and managing specific symptoms and complications. A variety of specialists may be needed to assist with various treatment protocols, including 55:

  • Medical geneticist
  • Ophthalmologist
  • Dermatologist
  • Hematologist
  • Gastroenterologist
  • Pulmonologist

Following an initial diagnosis, to establish the extent of disease and a proper course of treatment, the following are recommended if they have not already been completed 56:

  • Complete ophthalmologic evaluation
  • Skin examination for severity of hypopigmentation and, after infancy, for evidence of skin damage and skin cancer
  • History of bleeding problems and symptoms suggesting pulmonary fibrosis and/or colitis. For evaluation for lung fibrosis, pulmonary function tests (PFTs) should be performed in individuals older than age 20 years.
  • Consultation with a clinical geneticist and/or genetic counselor

For excessive bleeding, HPS patients may need transfusions of normal blood platelets. Women who have excessive menstrual bleeding (menorrhagia) can be treated with oral contraceptives.

The drug desmopressin acetate (DDAVP) can also be administered to patients with acute bleeding and has been proved effective for some patients. HPS patients should avoid blood anticoagulants, such as aspirin 57.

Patients with HPS types 1, 2, or 4 who develop pulmonary fibrosis may eventually need a lung transplant 58. For these cases, platelet transfusions should be used sparingly to reduce the creation of antibodies that could cause graft rejection.

Humidifiers may reduce the frequency of nosebleeds 59.

For vision issues, the majority of individuals with albinism have significant hyperopia (far-sightedness) or myopia (near-sightedness), and astigmatism. Correction of these refractive errors can improve visual acuity 60.

  • Strabismus surgery is usually not required but can be performed, although the surgery is not always successful.
  • Hand-held magnifying devices or bioptic lenses are helpful aids
  • Preferential seating in school is beneficial, and a vision consultant may be useful.

For pulmonary fibrosis, when it becomes severe, oxygen therapy can be palliative 61.

Several individuals with HPS1-related pulmonary fibrosis have successfully undergone bilateral or single-lung transplants 62.

Granulomatous colitis is similar to Crohn's colitis and may respond to steroids and other anti-inflammatory agents 63.

To minimize the impact of secondary complications it is recommended to seek protection from the sun, avoid cigarette smoke, wear a medical alert bracelet that explicitly describes the functional platelet defect, administer prompt treatment of pulmonary infections, immunize with influenza and pneumococcal vaccines, and get regular moderate exercise 64.

“There are also a lot of emotional, psychosocial issues, as well as taking care of children with this, taking care of adults with this, and helping family members. There's just a small group of people with HPS, so everybody knows everybody and just seeing when people pass away, what that does to the community, is also really challenging,” said Sferrazza.

“The psychosocial and emotional complications of this illness are pretty severe. And we can't forget about those things as well.”

The Prognosis of Hermansky-Pudlak Syndrome

The prognosis of a patient with HPS will depend a lot on what subtype they have. Some genetic mutations produce mild symptoms while others are life threatening 65.

“Everybody's different, depending on what their manifestations are,” said Sferrazza. “If you have a milder type of HPS, you could probably live a very long life, as long as you're not doing anything crazy, like extreme sports.

“Some people that are more mild lead very normal lives. They have kids through natural births. I've seen that happen. And they just know, I have this condition and I'm going to make sure that I'm doing my due diligence.”

However, with more severe forms, the prognosis can be less optimistic.

“People that are on the more severe end of the spectrum do live into their fourth, fifth, sixth decade, but with the assistance of a lot of drugs, a lot of therapies and with organ transplant, specifically a lung transplant.

“The prognosis wasn't as good, but we have a lot of different things we can do now. There was a drug that was experimental and was approved overseas, but not in the US. That has always been an issue for the individuals here in the US, is that there is this potential drug that may or may not help. That also was a big problem, because if it was helpful, those individuals were not getting and so you’re now dealing with an emotional psychosocial issue related to the availability of drug,” added Sferrazza.

“But this is a rare disease and with a lot of rare diseases, there's not a lot of research being put into it. … But again, the prognosis is better than it was. It depends on the type, but we definitely need a lot more research into potential treatments and therapies for these individuals.”

What to do Next: Living with Hermansky-Pudlak Syndrome

Education is a big key when dealing with HPS. Not only from a patient point of view, but from a medical professional point of view as well.

Information gaps are closing through the advent of advanced technologies, but doctors must still be able to correctly diagnose patients as early as possible so that effective treatment can begin. Raising awareness in the medical community remains a challenge.

Because there are so few cases in the world, finding an HPS specialist can also be challenging. One way to go about this is to connect into the Hermansky-Pudlak Syndrome Network.

“I wish the medical community would send patients to the network because not everybody's into support groups and that's okay. But people are very vulnerable and they have a lot of questions and I just think it's something that you just shouldn't have to go through alone,” said Kirkwood.

“A lot of times our people have difficulty getting genetic testing because the insurance companies don't distinguish what's one form of albinism to another. They don't because in the other forms of albinism, it's skin, it's vision, and it doesn't really matter if you have OCA2 or OCA3 or whatever. But it is really important to rule out Hermansky-Pudlak Syndrome because of the potential problems that can happen,” she added.

Sferrazza added, “I have been pretty pleased with the geneticists and genetic counselors when it comes to picking up this condition because they always do such a good job and their due diligence with family history, personal history.

They take the time to get to know the patient, the family, all the medical issues. And the availability of genetic testing is just so much different than it was previously.

“It is important, especially in the Puerto Rican population, to be asking ethnic specific questions. These diseases are really specific at this point to certain populations, even though it can happen to anybody, it's more common.

“You should put that ethnic background on the top of your pedigree to remember, some parts of Puerto Rico are closely aligned with Hermansky-Pudlak Syndrome. It’s the same thing with the Ashkenazi Jewish community and Hermansky-Pudlak Syndrome.”

“Also, the resources you give the patients are crucial to them understanding their disease and processing it emotionally, physically, and mentally. It is really important to provide supporting materials beyond a printed pamphlet from a lab. I'm talking about hooking people up with support organizations specific to their disease.

“Some of these rare conditions don't necessarily have that availability, but this one does. And the Hermansky-Pudlak Syndrome Network is a phenomenal group of people,” added Sferrazza.

Not everybody with HPS has a conventional way of being diagnosed which is why there are many resources at the HPS Network.

“They have Instagram, Facebook, and tons of social media presence. They can help people get tested, help people get appointments, direct them in the right direction of specialty providers. They've built an amazing community for individuals that are diagnosed., and individuals that are taking care of people who are diagnosed. It's really important to incorporate that as well into your genetic counseling,” said Sferrazza.

For More Information

Hermansky-Pudlak Syndrome Network, Inc. One South Road Oyster Bay NY 11771-1905 Phone: 800-789-9HPS Fax: 516-624-0640 Email: info@hpsnetwork.org www.hpsnetwork.org

My46 Trait Profile Hermansky-Pudlak syndrome

Platelet Disorder Support Association 8751 Brecksville Road
Suite 150
Cleveland, OH 44141 Toll-free: 87-PLATELET (1-877-528-3538)
Telephone: 440-746-9003
Fax: 844-270-1277
E-mail: pdsa@pdsa.org Website: http://www.pdsa.org/

The National Organization of Albinism and Hypopigmentation (NOAH) PO Box 959
East Hampstead, NH 03826-0959
Toll-free: 800-473-2310;
Telephone: 603-887-2310
E-mail: noah@albinism.org Website: http://www.albinism.org

Genetic and Rare Diseases (GARD) Information Center PO Box 8126 Gaithersburg, MD 20898-8126 Phone: (301) 251-4925 Toll-free: (888) 205-2311 Website: http://rarediseases.info.nih.gov/GARD/

National Association for Parents of Children with Visual Impairments (NAPVI) Phone: (617) 972-7441 Toll-free: (800) 562-6265 Email: napvi@lighthouseguild.org Website: http://www.napvi.org

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse One AMS Circle Bethesda, MD 20892-3675 USA Phone: (301) 495-4484 Toll-free: (877) 226-4267 Email: NIAMSinfo@mail.nih.gov Website: http://www.niams.nih.gov/

NIH/National Institute of Child Health and Human Development 31 Center Dr Building 31, Room 2A32 Bethesda, MD 20892 Toll-free: (800) 370-2943 Email: NICHDInformationResourceCenter@mail.nih.gov Website: http://www.nichd.nih.gov/

Referenced Sources

  1. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  2. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  3. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  4. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  5. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  6. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  7. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  8. Bonifacino, J.S. (2006). Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome. Annals of the New York Academy of Sciences, 1038(1): 103-114.
  9. Bonifacino, J.S. (2006). Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome. Annals of the New York Academy of Sciences, 1038(1): 103-114.
  10. Bonifacino, J.S. (2006). Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome. Annals of the New York Academy of Sciences, 1038(1): 103-114.
  11. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  12. Bonifacino, J.S. (2006). Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome. Annals of the New York Academy of Sciences, 1038(1): 103-114.
  13. Bonifacino, J.S. (2006). Insights into the Biogenesis of Lysosome‐Related Organelles from the Study of the Hermansky‐Pudlak Syndrome. Annals of the New York Academy of Sciences, 1038(1): 103-114.
  14. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  15. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  16. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  17. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  18. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  19. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  20. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  21. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  22. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  23. Izquierdo, N. J., Townsend, W., & Hussels, I. E. (1995). Ocular findings in the Hermansky-Pudlak syndrome. Transactions of the American Ophthalmological Society, 93, 191–202.
  24. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  25. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  26. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  27. Hurford, M. T., & Sebastiano, C. (2008). Hermansky-pudlak syndrome: report of a case and review of the literature. International journal of clinical and experimental pathology, 1(6), 550–554.
  28. Hurford, M. T., & Sebastiano, C. (2008). Hermansky-pudlak syndrome: report of a case and review of the literature. International journal of clinical and experimental pathology, 1(6), 550–554.
  29. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  30. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  31. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  32. Pozo, A., Yuste, V., Villar, A., Quintana, M., Navarro, F. (2002). Successful thyroidectomy in a patient with HPS treated with recombinant activated factor VII and platelet concentrates. Blood Coagulation & Fibrinolysis, 13(6):551-553.
  33. R. K. Poddar, S. Coley, & S. Pavord. (2004). Hermansky–Pudlak syndrome in a pregnant patient. BJA: British Journal of Anaesthesia, (93)5: 740–742.
  34. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  35. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  36. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  37. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  38. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  39. Izquierdo, N. J., Townsend, W., & Hussels, I. E. (1995). Ocular findings in the Hermansky-Pudlak syndrome. Transactions of the American Ophthalmological Society, 93, 191–202.
  40. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  41. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  42. Izquierdo, N. J., Townsend, W., & Hussels, I. E. (1995). Ocular findings in the Hermansky-Pudlak syndrome. Transactions of the American Ophthalmological Society, 93, 191–202.
  43. Izquierdo, N. J., Townsend, W., & Hussels, I. E. (1995). Ocular findings in the Hermansky-Pudlak syndrome. Transactions of the American Ophthalmological Society, 93, 191–202.
  44. Pozo, A., Yuste, V., Villar, A., Quintana, M., Navarro, F. (2002). Successful thyroidectomy in a patient with HPS treated with recombinant activated factor VII and platelet concentrates. Blood Coagulation & Fibrinolysis, 13(6):551-553.
  45. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  46. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  47. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  48. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  49. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  50. Wei, M.L. (2006). Hermansky–Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research, 19(1): 19-42.
  51. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  52. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  53. R. K. Poddar, S. Coley, & S. Pavord. (2004). Hermansky–Pudlak syndrome in a pregnant patient. BJA: British Journal of Anaesthesia, (93)5: 740–742.
  54. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  55. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  56. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  57. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  58. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  59. Huizing, M., Malicdan, M.C.V., Gochuico, B.R., & Gahl, W.A. (2017). HPS. European PMC, 133(2):128-134.
  60. Izquierdo, N. J., Townsend, W., & Hussels, I. E. (1995). Ocular findings in the Hermansky-Pudlak syndrome. Transactions of the American Ophthalmological Society, 93, 191–202.
  61. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  62. Brantly, M., Avila, N.A., Shotelersul, V., Lucero, C., Huizing, M., & Gahl, W.A. (2000). Pulmonary Function and High-Resolution CT Findings in Patients With an Inherited Form of Pulmonary Fibrosis, Hermansky-Pudlak Syndrome, Due to Mutations in HPS-1. CHEST, 117(1): 129-136.
  63. Grucela, A.L., Patel, P., Goldstein, E., Palmon, R., Sachar, D., & Steinhagen, R.M. (2006). Granulomatous Enterocolitis Associated with Hermansky-Pudlak Syndrome. The American Journal of Gastroenterology, 101(9):2090-2095.
  64. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.
  65. Huizing M, Malicdan MCV, & Gochuico BR. (2000). Hermansky-Pudlak Syndrome. GeneReviews, Seattle (WA): University of Washington, Seattle; 1993-2020.

Transcript

Olivia: You're listening to the Rare Disease Connection, a production of Aspect Health and raredisease.com. Something that I learned in my clinical genetics course is that there are not many people that have genetic diseases. They are rare, after all. However, the people that are impacted by these genetic diseases, whether it's a child diagnosed with a rare disease or a family that has a sister or a brother or a cousin with this rare disease, all of these individuals are impacted profoundly in a way that completely changes their entire life. I think that stuck with me because rare diseases are one in a million, but with almost 8 billion people on this earth, that would mean 10,000 people are affected. That, to me, is still a large community of people. Olivia: I think the sense of community is best highlighted by today's rare genetic disease, Hermansky-Pudlak Syndrome. The Hermansky-Pudlak Syndrome community is unlike one I've ever seen. So I am very excited to be talking about it today. Rare Disease Connection in our additional resources on raredisease.com and yourdna.com brings together the people whose expertise can explain what you're facing, from diagnosis to prognosis, to treatment options, all the way to questions like who do I talk to? Where are the people who have been through this before? You'll find those answers here from doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families, all within your reach. We're here to connect you. This is Rare Disease Connection. Olivia: Hey everyone. This is Olivia, co-host of Rare Disease Connection and genetic counseling summer fellow at yourdna.com. Today, I'm going to bring you conversations with three experts on Hermansky-Pudlak Syndrome or HPS for short. Before we get started, you should know that this podcast is just the beginning. We've taken the information from this podcast and added additional resources, explanations, links, and references for you in a downloadable guide. You can get your free copy by going to raredisease.com/hps. That's raredisease.com/hps. Olivia: So let's get started. Our first guest today is Lauren Giannetti Sferrazza. She is a certified genetic counselor. She currently works at Myriad Genetics as a Regional Medical Specialist in Oncology. As a graduate student at Long Island University, Lauren completed her master's thesis about Hermansky-Pudlak Syndrome. So hello and welcome, Lauren. We're so happy to have you here. Lauren Giannetti Sferrazza: Thanks so much, Olivia. I really appreciate the invite to come and speak about Hermansky-Pudlak Syndrome. I actually did complete my master's thesis on this topic and in particular, how it is so commonly misdiagnosed. My master's thesis was published as an abstract in the Journal of Genetic Counseling in 2014. And then I also presented the abstract as a poster presentation at the NSGC Conference in New Orleans in 2014 as well. Olivia: Yeah, that's really great. Could you tell me a bit about like your current position with Myriad? Because I know that's a little different than Hermansky-Pudlak Syndrome. Lauren Giannetti Sferrazza: Sure. I actually first started in the field of genetic counseling after I graduated as a clinical genetic counselor. I performed genetic counseling for fertility, prenatal and cancer patients. And this was all through telemedicine, which is now very popular, but it wasn't when I first started. And then I transitioned about two years ago to Myriad where I work in the oncology business unit. And I worked with a lot of different providers, such as surgeons, medical oncologists, gynecological oncologists, and genetic counselors in order to facilitate appropriate testing and risk assessment for patients that may be at risk for hereditary cancer syndromes. Olivia: Since HPS is such a rare disease, it's really hard to sort of find like a specialist in HPS. So thank you for coming in and being willing to share some of your knowledge from your master's degree. Could you tell us what some of the symptoms of HPS are? Lauren Giannetti Sferrazza: Sure. I think what's interesting to point out is that not everybody with HPS will present exactly the same. There are a lot of different subtypes and they just keep getting discovered as well. I think we're up to HPS10 at this point or even 11. I know one was just founded, a gene was just founded in the past few months, but I would say in general, every single person with Hermansky-Pudlak Syndrome, no matter the subtype, will have some sort of ocular albinism or ocular findings. So one of the things that you might see is called nystagmus. That is when you see somebody's eyes moving rapidly from side to side. Albinism is also a key feature, but not every person with Hermansky-Pudlak Syndrome actually has albinism. Albinism, meaning that they have very, very white skin, they have white hair, they usually will have very light-colored eyes. Obviously, because of the albinism, they can't be in prolonged sun exposure, that kind of thing, but not everybody with Hermansky-Pudlak Syndrome has albinism. And that's why it's misdiagnosed a lot. Lauren Giannetti Sferrazza: Kind of back to those key features. We mentioned that everybody has some sort of type of ocular albinism nystagmus, some sort of eye features. The other very key feature of Hermansky-Pudlak Syndrome is the platelet defect that these individuals have. And unfortunately, a lot of times this is also misdiagnosed as a clotting problem. It's not that they don't have the proteins for clotting or there's a mutation in one of the clotting factors, it's that their platelets are missing these what we call delta granules. And I like the way that the Hermansky-Pudlak Syndrome actually explains this. To all of the conferences they go to, they bring chocolate chip cookies and sugar cookies. And basically they are saying, they call this like the butter cookie effect. People who have normal functioning platelets have chocolate chip cookie platelets. Lauren Giannetti Sferrazza: There's granules, specifically the delta granules that can be visualized is under an electron microscope, particularly. It's very important to note that. And people with HPS have the missing granules and they have no chocolate chips. So their platelets look like sugar cookies. That's a very simplified way of explaining it, but I think it works. So because they're missing these delta granules in their platelets, they will have really high risk of bleeding and nosebleeds. When I was meeting with a lot of these individuals, when I would go to conferences, when I went to Puerto Rico, I would meet with a bunch of people. Some had albinism, some didn't, but everybody I met with said that they had some sort of nosebleed that they were having a hard time stopping. When they would go in for dental procedures it would be kind of really, really not a good situation. Childbirth was really dangerous for a lot of people. Lauren Giannetti Sferrazza: And it's really important in terms of like wound care, knowing about that it's a platelet issue. When you're going to the hospital with an emergency, these individuals need platelets. And that's a very, very specific ask. And the providers that are treating them need to know that because you don't want to bleed out. And there's been quite a few people that unfortunately have passed away due to these really severe bleeding issues. So I would say those are the two hallmark features of Hermansky-Pudlak Syndrome, where it really doesn't vary. Again, that is the platelet issue, which causes frequent bleeding, nosebleeds, and then the eye issue, the ocular albinism, nystagmus. Lauren Giannetti Sferrazza: On that spectrum, there are more mild types. So the more mild types maybe just have the ocular features and the platelet issues. And then the more severe end of the spectrum would be the albinism. There's also some colitis. So gastrointestinal issues as well. And then obviously, on the worst end of the spectrum would be the pulmonary fibrosis. And this leads to many people needing lung transplants. There's quite a few people that are in the HPS Network. It is a small group of people, but it's becoming larger. More people are being diagnosed. Thanks to the network, the foundation's efforts, and just them being visible to providers and at conferences. Lauren Giannetti Sferrazza: Quite a few people, unfortunately, have passed away due to the pulmonary fibrosis. This is almost kind of like the scarring of the lungs. So eventually your lungs are supposed to, when you breathe in, expand and contract. And if you have fibrosis, it doesn't allow the lungs to do that. The lungs become really kind of hard and people, unfortunately, are not able to breathe, which is really sad. You see a lot if people that are older that have this more severe type of Hermansky-Pudlak Syndrome, which is one of the more common types. HPS1 presents this way. A lot of people are on oxygen, they have oxygen tanks. And then they're on the donor list. Lauren Giannetti Sferrazza: And some people do receive new lungs. I'm still Facebook friends with a lot of those individuals. And I've seen that they've done pretty well with double lung transplant, but that is a whole another set of issues, getting on the transplant list, how long it takes. And obviously, some of these individuals are immune-compromised and can be very sick. And so sometimes lungs become available and then they are not fit health wise to have the lungs implanted. So it's really a challenging disease to deal with. There's a lot of different variability. And I think that's why it's so commonly misdiagnosed. Olivia: Yeah. I heard you mentioned pulmonary fibrosis and these bleeding complications with sort of routine like dental procedures, that sort of thing. Are those sort of the main complications associated with HPS or are there others? Lauren Giannetti Sferrazza: I would say that the main complications definitely are the issues related to bleeding because that happens basically to everybody. So if somebody gets cut, like if you're a little kid and you fall and you scrape your elbow, usually what do we all think? Okay. You clean it up and you throw a bandage on it. You don't think anything else. But people with HPS will continue to bleed through those bandaids. So having, usually what they taught me at the HPS Network was you gotta slap on some petroleum jelly. You have to put on some sort of petroleum jelly, vaseline. That's gotta be in your first aid kit because it creates a barrier. And then you've got to do a very specific pathway to treating that wound, even if it's just a small cut. That's a big difference, a bandaid versus using vaseline and gauze and all of these different things. Lauren Giannetti Sferrazza: So I would say wound care and the bleeding tendencies are definitely the biggest complication. Obviously, all of these people have eye findings, eye issues. So a lot of them need glasses. A lot of them cannot see. Some of them are legally blind. I'd say that's another complication. A lot of these people don't necessarily have a, and I don't want to say this in a negative way, but a normal life because they have so many medical problems in so many different organ systems. With the bleeding too, and I forgot to mention this, what's actually very interesting and a little sad is that a lot of kids that have this, obviously if they have lighter skin, if they have the albinism and they get a bunch of bruising, bruising happens a lot too. You don't necessarily have to get cut to your platelets not be working or whatever. If you bump, you get these huge bruises. And a lot of times when kids go to school with bruises, they start thinking that there's abuse happening in the home. Lauren Giannetti Sferrazza: So that's also important to have kids diagnosed early and set that up with the school. Otherwise, [DYFS 00:12:34] could be called then or other protective agencies of the state could be called in on these parents when really the kid just has this genetic condition that's really rare that causes them to bruise really easily and they have really little skin. That's also, I think, becomes a really big issue. Those are kind of the medical complex. There's so many more. Increased sensitivity to light. They really ... Not just SPF 30. We're talking SPF like 100, using hats, like really not going outside that much. And what's kind of very ironic about all of that is this is a condition that is super common in Puerto Rico, which when we all think of Puerto Rico, we think of beaches and warm weather. So these individuals have really hard time with covering up because that's their every day. It's very sunny in Puerto Rico. Lauren Giannetti Sferrazza: So I think that's also just changing their lifestyle. It's a big lifestyle change. It's a big change. It's not just, oh, well, they need an eye surgery or this or that. It's a multiorgan issues. And I'm sure I haven't touched on ... I just touched on kind of the top of all of these things. There's much more emotional, psychosocial issues, taking care of children with this, taking care of adults with this, family members. There's just a small group of people, so everybody knows everybody and just seeing when people pass away, what that does to the community is also really challenging. Lauren Giannetti Sferrazza: When I was presenting my thesis, one of my good friends who has Hermansky-Pudlak Syndrome was having a really difficult time. And she was waiting for her lungs to come in and be available. And there've been multiple lungs that were available and it just didn't work out because whatever reason. Organ transplant is not as easy as it might seem. And so that was really hard for me, to present my master's thesis on this topic and know in the back of my hand that my friend, she might not make it. She might be dying. It's really hard to know that and I don't even have the condition. So I think that the psychosocial and emotional complications of this illness are pretty severe. And we can't forget about those things as well. Olivia: Yeah. I mean, considering all these complications that you mentioned, there was sort of a spectrum of symptoms. What generally is the prognosis for an individual diagnosed with HPS? Lauren Giannetti Sferrazza: That's a good question. Again, it depends on the subtype. Everybody's different. Depending on what their manifestations are. If you have a more mild type of HPS, you could probably live a very long life, as long as you're not doing anything crazy, extreme sports. You don't get into any huge medical issue accidents. You don't bleed out or anything like that. So some people that are more mild lead very normal lives. They have kids. Natural births. I've seen that happen. And they just know, I have this condition and I'm going to make sure that I'm doing my due diligence. Lauren Giannetti Sferrazza: For other people that are on the more severe end of the spectrum, the prognosis is not great. I mean, people do live into their fourth, fifth, sixth decade, but with the assistance of a lot of drugs, a lot of therapies and with organ transplant, specifically lung transplant. The prognosis wasn't as good, but we have a lot of different things we can do now. There was a drug that was experimental and was approved overseas, but not in the US. That has always been an issue for the individuals here in the US, is that there is this potential drug that may or may not help. Again, this is a small subset of people. So when we're doing the study and you're looking at the end, the group of people, it's hard to say if it's statistically significant or not, but for a while, there was a drug that was being used overseas that wasn't available here. And that also was a big problem in general, because if it was helpful, those individuals were not getting and yeah, also another kind of emotional psychosocial issue of the availability of drug. Lauren Giannetti Sferrazza: But this is a rare disease and with a lot of rare diseases, there's not a lot of research being put into it. There's a lot of people who've read the NIH. Dr. Gahl has been a part of this syndrome for as long as I can remember. He's on the original papers about this condition, but it takes a lot of exposure, whether that be through social media, through Rare Disease Day, through different conferences, which I think Hermansky-Pudlak Syndrome, the organization does a good job on this. But again, the prognosis is better than it was. Depends on the type, but we need definitely a lot more research into potential treatments and therapies for these individuals. Olivia: How exactly does someone receive a diagnosis of HPS? Lauren Giannetti Sferrazza: This is what my thesis was partially about because it seemed like nobody was receiving it from a healthcare provider. It seems like most people were saying, "I have this issue, I have this issue and I have this issue and I wonder if they're all related." And they would be super savvy and going to Google. They would come upon the page for the Hermansky-Pudlak Syndrome Network and they would say, "Holy cow, I have this syndrome. Let me call Donna Appell. Let me go onto Facebook, Instagram." That's where the network has its presence. And they would come to the conference and there's a conference every year in Long Island, usually at the same hotel. And they would come to the conference and they would say, "Holy crap, I have this condition." Or, "My daughter has this condition." And they'd say, "The wait to meet with a geneticist is six months, but I know I have this and I'm going to come to this conference, I'm going to meet with these people to just become more educated." Lauren Giannetti Sferrazza: For me, what I found was that a lot of providers we're seeing these symptoms piecemeal. So they weren't putting it all together. Maybe when they went to the ER, the doctor would say, "Oh, you probably have a bleeding issue." But they never did the testing because it's a very specific test for the platelet issues. So they never looked further into it. They just said, "Oh, you've got factor something deficiency and you just have to make sure that ... Maybe you have hemophilia." There's a lot of times people were misdiagnosed. Just said, "Oh, you got albinism, that's it." But they never went further to say, "Oh, you have nystagmus. Oh, you have pulmonary fibrosis. Oh, you have bleeding tendencies." Lauren Giannetti Sferrazza: And that was part of my entire thesis, was that we need to do a better job as a healthcare system and as providers to identify these individuals. Just because you are an eye doctor, ophthalmologist or whatever, it doesn't mean that you don't ask about these other organ systems. If you see somebody that has this nystagmus and looks like they have albinism and starts to say, "Oh, I have bleeding issues and this and that." There really needs to be a lot of questions that are asked. And kind of the end point of my thesis was that every person with HPS has bleeding issues and has some sort of ocular manifestations. Lauren Giannetti Sferrazza: So we should really be making sure that either the hematologist or the eye doctors have this in their purview. I said specifically eye doctors because maybe not everybody has had a bleeding incident. There's cases where people just bruise really easily and that's it. And they're like, "Oh, I'm just like ..." But really at the end of the day, I called out that we need ophthalmologist, other eye doctor, other specialists in that field to be trained and to really start asking these questions. Because what is the journey to diagnosis? That depends on the person, that depends on how old they are. Nowadays, we're seeing younger kids that are picked up. Lauren Giannetti Sferrazza: When I went to the conference the first time, I think it was in 2013, we didn't have that many young kids there. There were older people that it took them 30 years to get a correct diagnosis, which to me is really crazy. You have these things and nobody's put them together. And that's kind of why the HPS Network started, because there was this collection of people that had this issue and nobody was talking about it. There's no published materials. There was not even a diagnosis code for this condition, which recently became a thing. They do now have a diagnosis code, which is a very big deal for billing and for insurance coverage and all of that stuff. Lauren Giannetti Sferrazza: But I mean, this was a bottom up effort by this organization, to get people diagnosed. So I would say, I would think most people are still being self-diagnosed there. They're googling. They're doing their due diligence. People now have availability to internet and HPS Network has obviously a website, which back in the day they didn't because that wasn't as big of a thing. But I think now I'm seeing younger kids being diagnosed because maybe they're seeing a geneticist earlier on because they know, "Hey, there's something going on here. I'm going to bring my kid to a geneticist." Whereas maybe many years previous, they'd just say, "Yeah, you got albinism. It is what it is." But bringing them to a specialty clinic has been really helpful. Lauren Giannetti Sferrazza: And some people can't afford genetic testing or can't afford appointments. So again, there were a lot of people walking around with Hermansky-Pudlak Syndrome that were saying, "I have this, but I never had a genetic test to confirm it." Or, "I'm waiting for my appointment." Because again, the genetics community, as you know, is inundated with appointments. To get a pediatric appointment, unless it's life threatening, can be a year, can be two years. I mean, it really depends on the backlog. And an adult condition where the person is being managed for all their issues, that could be a really long time wait as well. So I think that everybody's journey to diagnosis is very different depending on who you talk to. Olivia: Yeah. So I know earlier you mentioned Puerto Rico and that you yourself have gone and that HPS occurs more prevalently in this group. Is that accurate? And are there any other populations that kind of experience higher risk of having an HPS diagnosis? Lauren Giannetti Sferrazza: Yeah. That's a really good question. The last number that I looked at was for specifically Hermansky-Pudlak Syndrome type one and three. So one is the most severe form, very like the more common form. And three is the kind of more mild form where you would see just the bleeding issues and the eye issues and usually not the pulmonary fibrosis. Those two are very, very common in Puerto Rico. Those are usually found in the northwestern and central parts of Puerto Rico. Again, it's that island effect. The northwestern part of Puerto Rico, we would say the carrier frequency of Hermansky-Pudlak Syndrome. Again, this is a recessive condition, autosomal recessive. So you could be a carrier and obviously not have any symptoms, but the carrier frequency is one in 20, which is more common than cystic fibrosis. Lauren Giannetti Sferrazza: When I was doing my research, I tried to bring it back to a lot of providers that we talk about cystic fibrosis. We have so many organizations and we talk about this because it's common to the Caucasian population and other populations as well. But the carrier frequency of CF is like one in 25, one in 23, depending where you look. HPS type one in Puerto Rico, in northwest Puerto Rico is about one in 20. And then in general in Puerto Rico, the frequency of Hermansky-Pudlak Syndrome is about one in 60. Olivia: Wow. Lauren Giannetti Sferrazza: That's the carrier frequency in just Puerto Rico. That is really common. We screen for conditions that are way more common than that in general. And this is to my knowledge, and maybe this has changed, but the last time I had looked, this was not part of newborn screening in Puerto Rico, which is really disheartening since it is such a common condition and it really does need intervention as early as birth for that individual. So it is very common in the Puerto Rican population. It's also common in the Ashkenazi Jewish population. Again, Ashkenazi Jewish populations do have quite a few conditions that they are more at risk for. Lauren Giannetti Sferrazza: Again, just like Puerto Rico, kind of that population effect where if you are continuing to have partners within the same population, there's not that genetic diversity. And here in Puerto Rico, it's an island effect. So people don't necessarily leave the island. Important thing that I learned from Donna Appell was that there are more Puerto Ricans in New York now than there are in Puerto Rico. So, if I'm saying that should be part of Puerto Rican newborn screening, this really should be part of New York newborn screening. Olivia: Exactly. Lauren Giannetti Sferrazza: There's a lot of Puerto Ricans in New York as well. The most recent population that I learned about was actually, and I want to make sure that I get this right, the Japanese population. Hermansky-Pudlak Syndrome, I believe, has been identified in 15 different countries. And when they have the meetings and when they look at all of their network of people, there are people from 35 different countries that joined these meetings. In, I believe it's Japan, Hermansky-Pudlak Syndrome is being the common cause of albinism in the Japanese population. So I think that that's really interesting in general. And that was not something, when I did my thesis, that was in 2014, it wasn't that long ago that we did not have that information yet. So now with more information, more people being diagnosed, more resources, we're abl to start looking at other populations in general, to see that this is actually maybe more common than we initially thought. Olivia: You mentioned that it's an autosomal recessive disorder. Could you just briefly describe what autosomal recessive means? Lauren Giannetti Sferrazza: Sure. And I wanted to correct something I said before. It's the second most common type of albinism in Japan. I said it was the most common. It's the second most common, which is it's still significant. Autosomal recessive inheritance means that we all have two copies of every single gene in our body. Our genes are important for different functions. When it comes to autosomal recessive inheritance, we have again, two copies of every gene. So we get one from mom and one from dad. And when we're looking at these genes associated with Hermansky-Pudlak Syndrome, let's say the HPS1 gene, we're going to get one copy from mom and one copy from dad. If for some reason, both of those copies, the one from mom and the one from dad, have the mutation, something in the genes that is going to make it nonfunctional and you inherit both copies of those, it then doesn't allow you to have any functioning HPS1 gene. Lauren Giannetti Sferrazza: So the function of that gene is completely knocked out. You don't have a backup copy. So you then manifest symptoms of this disease. Just thinking about what are the risks for other siblings or other people in the family, this is not something that if you're a carrier you'll know, unless you do genetic testing carrier screening or unless that there's a family history. So if I have HPS, both of my HPS1, let's say, genes don't work. And there's a 50/50 chance that I would pass on either copy to my child. So since I have no working genes, there's 100% chance my child will inherit a gene that doesn't work. So they will automatically be carriers. Lauren Giannetti Sferrazza: Now, if my partner let's say my husband, he's a carrier of Hermansky-Pudlak Syndrome. He also has, he has a 50/50 chance of passing down one of his genes. That's how it works. And there's a 50% he would pass down one of his non-working copies. So it is important, looking at people with Hermansky-Pudlak Syndrome, their children will always be carriers at least. Some of them that might be affected if those individuals are having children with people that also have Hermansky-Pudlak Syndrome or are carriers, which happens. Or if two people randomly come together and just randomly carry it, which has happened a lot. Lauren Giannetti Sferrazza: That's the story for Donna Appell and her husband. They had no clue that they both carried a mutation in their HPS gene. They met, they came together. It wasn't like we had that type of genetic testing. And also, you don't ask those questions on first dates. And they got married and they had a child. Their first child was a son, completely normal. I'm not sure what his status is, but he doesn't have HPS. And then they had their daughter Ashley and she is affected with HPS. I believe she has HPS1. How that worked was they were both carriers. There was a 25% chance that their child would inherit both copies of their genes that didn't work. The majority, if we're going with odds, is that they wouldn't have a kid with HPS, but they did. They had one kid that didn't, one kid that did. Each new pregnancy, each new child is a new risk. So just because they have their son who doesn't have HPS, doesn't mean that they wouldn't have another child with HPS. Lauren Giannetti Sferrazza: So every single pregnancy, if you're both carriers, would be a 25% chance or one in four chance, which depending on what you're thinking about, it doesn't seem that high, but it's still a good chance. And it's still something that is good to know about in advance. There's a lot of people that didn't know they were carriers or didn't know this condition was in the family until they had a child that was affected with it. And that's what we see quite a bit as well when you go to those Hermansky-Pudlak Syndrome conferences. Olivia: Yeah. In closing, what's something that you think is important for genetic counselors or geneticists, kind of like medical professionals, to know about HPS? Lauren Giannetti Sferrazza: I would say in terms of the symptoms, it's really important to recognize this condition. I have been pretty pleased with the geneticists and genetic counselors when it comes to picking up this condition because they always do such a good job and their due diligence with family history, personal history. They take the time to get to know the patient, the family, all the medical issues. And the availability of genetic testing is just so much different than it was previously. I would say, genetic counselors, it's really important to remember this, especially in Ashkenazi Jewish families, in Puerto Rican families. I think I was the only person for a long time that when somebody was Puerto Rican and I was seeing them for carrier screening, I would ask, "Does anybody in your family have bleeding issues? Nystagmus? Eye issues? Albinism?" Lauren Giannetti Sferrazza: And they would look at them kind of sideways, but it is important, especially in the Puerto Rican population, to be asking these ethnic specific questions. These diseases are really specific at this point to certain populations, even though it can happen to anybody, it's more common. So to just start thinking about, when you put that ethnic background on the top of your pedigree to remember, okay, Puerto Rico, Hermansky-Pudlak Syndrome. Same thing with Ashkenazi Jewish, Hermansky-Pudlak Syndrome. So that's the one of the big takeaways I would want a genetic counselor or a geneticists to have. Lauren Giannetti Sferrazza: The other one is that resources you give the patients are crucial to them understanding their disease and processing and being able to just really get it emotionally, physically, mentally. It is really important to provide supporting materials. And I'm not just talking about a printed off pamphlet from a lab. I'm talking about hooking people up with support organizations specific to their disease. Some of these rare conditions don't necessarily have that availability, but this one does. And the Hermansky-Pudlak Syndrome Network is a phenomenal group of people. It's run by Donna Appell and a lot of wonderful supporting ladies that have been there for a very long time. I was thinking too, while I was preparing for this podcast, what's something about people with Hermansky-Pudlak Syndrome that I want everybody to know about. Lauren Giannetti Sferrazza: And it's just, they're the nicest people I've ever met. They have some of the worst medical conditions that I've seen. I mean, just think about the pulmonary fibrosis and knowing that that's coming. These are the most pleasant, the happiest, the nicest people, the most generous people that I've encountered. And that's why it just breaks my heart that a lot of them didn't get they deserved or needed and that they were misdiagnosed for so long. But I would really want medical professionals in general to take away that these support groups are so crucial for these individuals to create a community, to feel like a part of a community. Lauren Giannetti Sferrazza: A rare disease is rare. So people start feeling singled out and that they don't have anybody else that they can confide in or talk to. And this is a group of people that knows exactly what everybody else is kind of going through and they are just a wonderful resource. So I would say it's really important to whatever disease that you're diagnosing somebody with, to make sure that you do that extra legwork and find the support organizations, even people that are waiting for an appointment and it says, "Potential Hermansky-Pudlak Syndrome rule out." If their appointment is not for another six months, you can reach out to them and say, "Hey, if this is what you're thinking, this is a good place for you to start learning about it before our appointment." Lauren Giannetti Sferrazza: I know that's kind of a weird thing, but again, not everybody with HPS has a very conventional way of being diagnosed. And there's just so many resources at the HPS Network. They have, again, Instagram, Facebook, tons of social media presence. They can help people get tested, help people get appointments, direct them in the right direction of specialty providers. Again, it's a rare disease, but they've built an amazing community for individuals that are diagnosed, individuals that are taking care of people that are diagnosed. So I think it's really important to incorporate that as well into your genetic counseling. Olivia: Yeah. And HPSN is definitely an invaluable resource, especially in Long Island where it's so close to where we are. But I just wanted to thank you again, Lauren, for joining us today. But whether you've interacted with a genetic counselor yet or not, they play a really invaluable role in the journey of anyone diagnosed with a rare genetic disease. If you have questions about Hermansky-Pudlak Syndrome, I would really recommend looking at nsgc.com to find a genetic counselor near you. Olivia: Today we have Donna Appell as a guest. Donna is a registered nurse who is the Founder and Executive Director of the Hermansky-Pudlak Syndrome Network. This is based out of Oyster Bay, Long Island. HPSN is the only patient support organizations specifically for HPS. It was founded in 1992 and has been working incredibly hard for the HPS community that includes her lovely daughter. So hello and welcome, Donna. Donna Appell: Hello, and thank you so much for having me. I'm very honored and excited to be here, talking with you, distant talking with you, and grateful for the opportunity. Olivia: Of course, we're so excited to have you. To start, could you tell me a little bit about yourself? Donna Appell: Well, I'm rarely Donna. I'm more often Ashley's mother and I'm very honored to be that mother of her, but my journey in life was to become a nurse. I went to school and I'm an RN and I was that working and before I ever had Ashley. And I kind of think that it might've come in a bit handy, since I wasn't expecting a child as Ashley, but I live on Long Island. I have a son as well as my daughter. And they're both the light of my life. And I have a great husband and I work very hard, worked for 22 years in an intensive care unit and have worked 27 years in the Hermansky-Pudlak Syndrome Network. As the Executive Director of the HPS Network, I am pretty much a 14-hour day work quite often. That's the usual amount of hours in a day here because I really am frenetically trying to cure this disease, which is a really lofty goal and not quite coming to fruition. It's taking forever. Olivia: Yeah, you're extremely committed, you and everyone at HPS. I very much admire that about that community. So speaking from your experience as Ashley's mother, mother of someone with HPS, what immediately comes to your mind when you hear Hermansky-Pudlak Syndrome? Donna Appell: I am really scared about it. I kind of, I'm worried. In HPS type one, two and four, it's fatal. And my daughter has HPS type one and I am terrified. I kind of think that ... I make a joke sometimes that some people need Prozac to calm themselves down and I need a Proact instead. I needed to just keep trying to fix this. I couldn't be a barnacle on a log and let it all happen to me. I had to do something to fix this. It's almost pathologic in a way. It drives me so much that I have a little harder time relaxing than I do working. My comfort zone is at the HPS network, working hard to try to find the cure because I figure I could outrun it. Olivia: Yeah. Yeah. And I think that's something that's also really seen in how hard HPSN is working, is that you're really translating any type of fear, anxiety into doing something and really committing to finding a cure. Could you spend some time kind of telling us about your daughter and what is it like being her mom? Donna Appell: Oh, it's crazy good. Ashley was born and we discovered that she had albinism at her two-week well baby visit when they really looked in her eyes and felt like she was a child that had albinism. And that was pretty upsetting to us, of course, because she was legally blind and they said that she would never drive and nor does she. And it was pretty much hard to get over. And I guess around 12 months, when she started to really try to walk around, when she tried to learn how to walk, I noticed these bruises on her shins. And I'm like, what are these little bruises? You're on the carpeting. There's nothing to get bruised about. Donna Appell: So I started, I took her to the pediatrician. That's when they told me, well, her skin is fair because she has albinism. So her skin is fair. So that's why you see bruises more. And I'm like, well, that's utterly ridiculous. It's either a bruise or it isn't a bruise. It doesn't matter what color your skin is. So I kind of really felt very patronized and went back and forth a couple of times and still got very patronizing answers. So I started to research about albinism and just was reading a pamphlet that had one sentence about a platelet defect. And with that, I called the author. I just called up the author, which was pretty bold of me and it's not like me at all. And he sent me a test tube and we drew Ashley's blood and sent it back to ... We live in New York. We actually sent it to Minnesota. Donna Appell: And there, he checked her blood, her platelets and called us and said that she had Hermansky-Pudlak Syndrome. At that point, they said that because we are not of Puerto Rican descent way back then, they said, this is a misnomer that because we're not a Puerto Rican descent, that it would be a mild bleeding disorder, nothing, no problem, just go procreate. The reason why Puerto Rico comes up is because there's a genetic founder's effect on Puerto Rico, so that it's very prevalent on that island. And the myth was that was a more severe type of HPS than we could possibly have. Donna Appell: Needless to say, at two years old, my daughter hemorrhaged to shock in her crib from the bowel disease of HPS. So she was rectally bleeding terribly and ended up in the hospital for three months. And it was our journey into the severity of Hermansky-Pudlak Syndrome. My husband and I were so isolated from that event because everybody was saying, they never heard of this, they never saw this before. All the doctors were saying, "I've never taken care of anybody with this." Which is a terrifying feeling that a family could be going through. It's very isolating. So we decided to incorporate and start the Hermansky-Pudlak Syndrome Network from then forward. Donna Appell: Ashley has been a dream. She's just been the most resilient, most unbelievable human I have ever met in my life. I mean, she's just so resilient and so filled with light. I mean, she's just not a complainer. She just is an example to everybody. I call her a pebble. She's the pebble in the pond that just ripples out from there. And she certainly does it in the HPS community, but she does it in our church community. She's gotten through school by hook or by crook, even though it's taken her a long time because of all of her absences and her illnesses, but she graduated and she's a preschool teacher and she's the light of her classes and the children. And she's just an amazing person. And I get inspired by her every day. Olivia: That's amazing. And I think it's important to remember too with that, that part of the reason why she came out so amazingly is because she had you and your husband, her brother all as supports. But I know there's just a world difference from now and the time Ashley was born in terms of what's known about HPS. But if you could go back in time, knowing what you know now, what's something you wish that you had known about HPS that could have been helpful for you and your family back then? Donna Appell: Sure. I'd love to mention that, but I think the caveat is I don't think much has changed personally. I wish I could say, "Well, now, if she was born today, things would be different." And I got to say that because rare diseases and we're kind of ultra rare, but these rare diseases are still not really that much known more than back then in a way. What I would have loved to have known is that when she hemorrhaged at two years old, she needed platelets much more than she needed blood. And it would have prevented the hypoxia, the lack of oxygen to her head, which she ended up getting a traumatic brain injury from the lack of oxygen from the hemorrhaging. And if we had known, understood more about Hermansky-Pudlak Syndrome and more about how to take care of her, I know that we could have prevented a traumatic brain injury. She's now an amazing individual, but she's a dependent adult. She has this traumatic brain injury and executive functioning problems. So she's pretty much stuck with me because we're a team. Olivia: You established the Hermansky-Pudlak Syndrome Network so you could create this community of individuals that really needed the support that you and your family were lacking. And it is the only nonprofit worldwide for the syndrome. So could you tell us a bit more about HPSN and some of the work you're doing? Donna Appell: Sure. We're really a tight and kind of an incredible little engine that could. We are certainly super poor. We really don't have a lot of money. It's very hard in some ways to get a lot of fundraising with this type of disorder because people are not only chronically ill, but they're also disabled. They're also legally blind. That becomes difficult to become super big earners in the job market when you're battling your chronic illness and have a legal blind issue and transportation problems and everything that goes with that. So fundraising becomes difficult. We're also probably largely, even though it occurs in every nationality around the world, we are international and we have members from 35 countries and 10 other reported country. So it's in 45 countries that we know of, but it's very prevalent among the Puerto Rican people. So we have Spanish and language issues. We have all sorts of things going on. Donna Appell: So it makes sense a little bit of a hard time getting a lot of funds behind us. But nonetheless, we are a very powerful little group and we're just really proud to say that we became one of the 30 organizations that were approved and awarded a grant from the Chan Zuckerberg Initiative. So we are one of the Rare As One organizations and super excited about learning with that group of other 29 organizations. And we're kind of like an incubator group on trying to figure out how to make cures and treatments come faster for rare diseases and Chan Zuckerberg's Priscilla Chan is like, she's my new idol. She's just amazing. Donna Appell: Some of the really crazy stuff we've done ... That kind of just started, but before that we were rocking with things like we really wanted to ... We know that our role as a rare disease organization is to create a super clean, clear, characterized cohort of research ready individuals. So our job is to kind of really train our people what it means to be in a clinical trial so that we're research ready. What is informed consent? What is a placebo? These are things that are foreign to people that are involved in research. We have a curriculum that we do a pre and post test and we deliver. And then we go a step further in an individual research plan and individually talk to a member and find out what is their interest in research. Do they want to be a part of research? Are they willing to do just surveys or are they willing to give us tissue? Are they willing to give us their healthcare proxy's name should something happen to them? Could we have some autopsy? Donna Appell: It's a very in depth project that we do to make sure that all things are ... I's are dotted and T's are crossed to be able to get involved in the research so that people are not dealing with it when crisis hits. So we want things like the explants of lungs. When people are going for a lung transplant, we want the old lungs. We want things like that. And it needs to have a proactive approach to be able to get the family behind this so that they're not doing this while they're all stressed. Donna Appell: Another crazy thing that we do as a group is we kind of really feel like a little, I guess, encumbered by the idea that the research protocols and researchers and stuff wait for us to trollop into the clinics to be able to be involved in whatever they're doing of research, blood draw or whatever it is. And I always feel like it's a burden to our families because A, they don't drive. Nobody's got transportation nailed down. And it means not only them taking a day off from work, but it means their caregivers taking a day off or their drivers taking a day off and waiting for these appointments to be made and the whole yada, yada. That's why cures never come along. So we actually said, "Come to us, come to the people." Rather than having people come to the research. Donna Appell: At our conferences that we've had annually, we actually have this program called We're Drawn Together and we invite academic centers to give us, get their IRBs, their own personal IRBs approved, to come to the conferences and draw specimens, get blood, get poop. We've done it all. We've gotten urine. We've gotten all sorts of things. And one year we had five different academic centers, all with five different informed consents that needed to be done within large print and translations. We needed to deidentify everybody. We needed to get this done in a very short period of time because it was for STEM cells. One of the projects was for STEM cells. So we only had a two hour window of time to get this blood to the lab to get spun. And we were able to accomplish 98 specimens in an hour and 55 minutes. Olivia: That must be a world record. Donna Appell: It is. It is world book record, certainly for people with albinism, to get that, right? Olivia: Yeah. Donna Appell: So that's kind of what we're doing. We're super active, super busy. While this pandemic is going on we wanted to keep research going so we're working on, in collaboration with the NIH we're working on a symptom scale study so that we're making this really big survey and qualifying the survey for determining the symptoms that like trickle up to the top for our people so that we can make sure that it informs research properly and we're doing what the people need us to do. Olivia: I think it's really hard to hear this stuff and not get excited and not want to get involved. How can people outside of HPSN help your goals and get involved with the advocacy work? Donna Appell: Well, one thing is that I would ... Thank you so much for asking that question. That's a good question. You could all come and help us. No. I think that one of the things that's my dream and I feel like I can't die until it's done is that I need to get the standard of care for children born with albinism to be screened for this rare disorder. So that's something in genetics, genetic testing world. Unfortunately, getting genetic testing is sometimes out of the possibility of some people. It's not covered by insurance. We have all these barriers in the way of getting gene testing. So a diagnosis of albinism can be given based on the fact that people are wearing it on their skin. So a baby's born and they have albinism and they have nystagmus, which is an involuntary eye jiggle. Donna Appell: And then they're sent packing with the diagnosis of albinism. And yet, in fact, the possibility exists that these people are sent home and these children might get a fever and some pediatricians actually prescribing Infant Motrin, which is totally contraindicated for the bleeding problem of HPS. So one of the things is to, an awareness is to make sure that people know that everybody born with albinism should be immediately screened. We do all these newborn screenings, like 47 per state or whatever of these newborn screenings, yet we don't ever screen a child born with albinism. Or for that matter, since people of Puerto Rican descent can have a lot of color, they could have a little darker skin and they could have brown hair and brown eyes. They don't look like they have albinism. Donna Appell: So I would say when you have a congenital nystagmus and you don't have a neurological origin for that, then they should be screened for Hermansky-Pudlak Syndrome. And that's not at all done. So changing the standard of care would be super helpful. And getting the opportunity to talk to you and having this advocacy, this outreach go out, someday somebody is going to be able to change that for us, I hope. Olivia: Definitely. I think that's part of what you said, when Ashley was born, people just didn't know about HPS and still, it is on geneticists, genetic counselors to really educate themselves about rare diseases like HPS so we can provide proper care. Lastly, what's one thing you wish everyone knew about HPS? Donna Appell: I guess how prevalent it is. You kind of think it's like super like, I've never heard of it before or whatever. But I'll tell you that it has the same incidence as cystic fibrosis. And you've heard of that. In the European or Caucasian population, the incidence, the disease is cystic fibrosis. And it's in every other nationality, but it's really prevalent in that one. The same goes with like sickle cell to people of African American and Tay-Sachs for Jewish people. This is HPS for Puerto Rican people and the incidence is the same, but nobody's heard of ours. Nobody's heard of HPS. I think what I really like everybody to know is that there's a real big healthcare disparity here. And I could really appreciate and use a bunch of soldiers out there to get the word out about Hermansky-Pudlak Syndrome, because we need the outreach. We need people to be aware of it just as they're aware of the diseases that have similar incidents. Olivia: Okay. In an effort to help get the word out about HPS and educate people, could you plug all your stuff? Where could we find you on social media? Donna Appell: I would love to. On Facebook we're HPSNetwork. All one word. Instagram, we're @HPSNetwork. And our website, it is www.hpsnetwork.org. And we would be really excited to have any visitors of any kind and friend us, please. We're very, very friendly group. I think actually happiness and humor is part of the coping of our disease. And people have said that it must be part of the gene because everybody in the network, all of these people with HPS are the sweetest, sweetest, most loveliest people you could ever want to meet. Olivia: That is most definitely true. Thank you so much, Donna, for joining us today. If you or someone you love has a diagnosis of HPS, you are most definitely not alone. The HPS community is small, but they are very mighty. So check out hpsnnnetwork.org for more information and resources. Our final guest is Heather Kirkwood. So Heather was diagnosed with HPS in her 20s and she is an extremely active part of the Hermansky-Pudlak Syndrome Network as their Chief Operations Officer and Director of Communications. Hello and welcome, Heather. Heather Kirkwood: Thank you. Olivia: Yeah. I'm really excited to have you on. Heather actually has a degree in journalism, so she's going to be better at this than I am. But really quickly, Heather, do you mind introducing yourself and telling us a bit about your involvement with the HPS community? Heather Kirkwood: Yeah. Currently I'm the Director of Communications and Vice President. So I do a lot of our communications and outreach to patients and talking to new patients and getting them adjusted into the community and helping them kind of go through that process. Olivia: Yeah. Could you tell us a bit more about your personal experience with HPS? Heather Kirkwood: Sure. My brother and I both have HPS and we weren't diagnosed ... I wasn't diagnosed until I was 29. I had really bad bowel disease in college and ended up having to have an ileostomy. And thank God, there was a hematologist who my mother had said, somebody had told her that her kids might bleed. So she needed, if there is anything serious to happen, she needed to get a hematologist involved. So I was very, very ill and my mom's like, "We have to get a hematologist." This is before the internet was the way it is now. So this guy like cancels his appointments for the day, goes into the medical library, comes back after a days of research with this book and this little paragraph. And he's like, I think if we give you some platelets, you'll be fine. That wasn't really a diagnosis or anything, but anyway, thank God. Olivia: Yeah. Heather Kirkwood: Very lucky because I don't think I would've survived that surgery if he hadn't given those platelets. After that, I was frankly kind of sick of dealing with medicine and medical stuff that I was healthy and doing fine. So I didn't think much of it. I just kind of went on with my life until I was 29. Actually, I had a sinus infection, which has nothing to do with HPS, but I couldn't get rid of it. So I went to ... A friend of mine was a nurse. I went to a doctor that she worked with for a second opinion, and on the medical history, I wrote down Hermansky-Pudlak Syndrome. And the doctor, after a week, went to all the stuff for the sinus infection. She says, "What is this about this Hermansky-Pudlak Syndrome? What is that?" And I was really embarrassed that I really didn't know. I hadn't as much time looking it up as I would news story I did on any given days. Heather Kirkwood: I went back to my office and googled it and started pulling up these papers that said, "You usually fail in the third to fourth decade." And yada, yada. I, of course, got upset and called my mom who got upset. Called my aunt, the sane person in the family she got online and found Donna and called me back at work and said, "You need to call this lady." So I found an office that wasn't being used and called her immediately. And I was at the NIH like three months later, got an official diagnosis of Hermansky-Pudlak Syndrome. Olivia: That was quite the journey then. Heather Kirkwood: Yep. Olivia: So the hematologist at that very first surgery, when you were 29, 28, 29. Heather Kirkwood: 19. Olivia:

  1. Okay. So he didn't suspect Hermansky-Pudlak Syndrome, but he kind of knew it was some sort of platelet that you needed. Was that correct? Heather Kirkwood: No, he thought it was Hermansky-Pudlak Syndrome. That's what he found in this book. Olivia: Okay. So that's where you kind of first heard of Hermansky-Pudlak Syndrome. Heather Kirkwood: Right. Olivia: What was it like growing up? You said you and your brother both have HPS. So growing up, did your mom always think something was going on or? Heather Kirkwood: There were a couple of bleeding instances over the years. We were worked up for bleeding disorder like four times and everything came back normal. But by the grace of God, we never had anything serious happen. Olivia: Yeah. Heather Kirkwood: I tell people like, the scary is not having Hermansky-Pudlak Syndrome. It's having it and not knowing it because you can't treat it. Olivia: Yeah. So what does a day in your life look like? What is everyday for you? Heather Kirkwood: I received a single lung transplant about two and a half years ago. That is trading one disease for another, definitely. I mean, I kind of knew that going in, but it's definitely been that way. Right now I'm having some rejection. So to treat that, they have really immunosuppressed me. Probably why I have this thing going on right now. So I have to be very careful of like ... Because everybody's wearing these masks as if it's a new thing and that's what I do all the time. But I would say before the transplant, there are certain sort of milestones in people's lives that are real markers. First, it's getting the diagnosis and then it's when you start having trouble breathing. And then it's when you have to go on oxygen. And then it's deciding if you want to go for a lung transplant or not, which is a big decision, requires a lot of planning and fundraising. Olivia: Yeah. Heather Kirkwood: And then after transplant, you've just traded this one disease for another one. Olivia: Can you tell me a bit about what it's like to live with the transplant? Heather Kirkwood: Yeah. I think the hardest thing living with the transplant that I didn't fully appreciate, I guess, is the immune suppression and how ... You have to be so careful. There's all these food rules. So you can't have like a salad out in public because you can't be sure that the lettuce has been washed thoroughly. They tell us not to ... You know smoothies are like a big deal right now. There's smoothie places everywhere. And we're not supposed to do those because you just don't know if the fruit was washed. When I eat out, I try to eat something that's like cooked. Olivia: Yeah. Yeah. It sounds like you just have a lot more ... Even before the transplant, when you had HPS, there was a lot more that you had to think about that other than people didn't and now it's even more so with the transplant and with coronavirus going on. So I'm sure, yeah, I'm sure that is definitely a concern for you. Heather Kirkwood: I've been in germ jail since November. So I have no empathy on like you. Olivia: Yeah, no. We're all in this now. What's something that people seem to misunderstand about you? Heather Kirkwood: I think sometimes people don't realize the vision issue because we adjust to it so well. Most people with HPS are legally blind. Not all. Some have vision issues, but they're not legally blind, but most of us are legally blind, but we still see quite a bit. We have quite a bit functional vision. So I think sometimes people don't realize, don't appreciate that, don't appreciate what we can see. It's funny because even people you've lived with your whole life, your parents and such don't fully appreciate sometimes what you can see and can't see. My brother and I have this sort of inside joke. When we were kids we'd driving in the car. We lived in Colorado. And then my mom would go, "There's deer. There's a deer. Look, right there. He's right there." So we just thought, so we would say, "We see it." Olivia: We also, we love looking at the deer too, mom. Heather Kirkwood: We're [inaudible 01:05:04]. Olivia: Oh, that's so funny. With your vision symptoms, was this apparent then, since you had these since you were a child, this didn't- Heather Kirkwood: Yeah, so since birth. It was very apparent from birth that we had albinism. It just wasn't ... Genetic testing has come a long way since the '70s. We just weren't aware of what type of albinism we had. Olivia: What's something you wish that the medical community knew about HPS? Heather Kirkwood: I wish that the medical community would send patients to the network because not everybody's into support groups and that's okay. But people are very vulnerable and they have a lot of questions and I just think it's something that you just shouldn't have to go through alone. A lot of times our people have difficulty getting genetic testing because the insurance companies don't think what's one form of albinism to another. They don't because in the other forms of albinism, it's skin, it's vision, what doesn't really matter if you have OCA2 or OCA3 or whatever. But it is really important to rule out Hermansky-Pudlak Syndrome because of the potential problems that can happen. Olivia: Yeah. And I think it just goes to show like even today, like you said, we have Google, we have the whole world at our fingertips really. And there are still doctors and geneticists that don't know about Hermansky-Pudlak Syndrome. So raising awareness even just about what is HPS is really important. Heather Kirkwood: And the other thing I'll say is it's so rare that you don't have to worry about it. Well, if you already have albinism, you've already breached a certain level of rare. Olivia: Yeah. Yeah. And I think Donna put it in a really good perspective where yeah, worldwide, HPS is rare, but in Puerto Rico, the occurrence rate of HPS is the same as like cystic fibrosis. And that's a disease we hear about all the time. So that really put it into perspective for me. Heather Kirkwood: Well, and people wouldn't think of ... If they saw me, they wouldn't think of Puerto Rico. And actually, I do have some Puerto Rican ancestry, my great grandfather was from Puerto Rico. But that's one part of the family tree. The rest of us is German, Scottish. Olivia: Right. What do you wish everybody, everyday people, what do you wish they knew about HPS? Heather Kirkwood: Well, I mean, even though we live with this disease, you have a lot of anxiety kind of building up to it, especially I should say, if you have types one, two or four, because the other types don't cause the lung issues. And even though we have vision issues, we still lead very productive and happy lives. Olivia: Yeah, definitely. Thank you so much for sharing your story with us and speaking about your experience with HPS. For a lot of individuals, the diagnostic journey can be long. But don't give up. To connect with other individuals like Heather or even families with Hermansky-Pudlak Syndrome, you can visit hpsnetwork.org. Olivia: In closing, we have had the chance to talk to three experts today in Hermansky-Pudlak Syndrome, but this is just the beginning. We've taken all the show's information and included it in a free downloadable guide. You can get your free copy by going to raredisease.com/hps. We would love to connect with you. If you need someone for standing by go to raredisease.com/help. We're waiting for you. Rare Disease Connection is a production of Aspect Health and raredisease.com. Thanks for joining us.

Clinical Trials

Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

National Institutes of Health Clinical Center (CC)

Learn More on ClinicalTrails.gov

Medical Treatment of Colitis in Patients With Hermansky-Pudlak Syndrome

National Institutes of Health Clinical Center (CC)

Learn More on ClinicalTrails.gov

A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis

Vanderbilt University Medical Center

Learn More on ClinicalTrails.gov

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