Author and Contributing Experts to this Guide include:
Brenna: You're listening to the Rare Disease Connection, a production of Aspect Health and raredisease.com. Brenna: Our bodies are incredible displays of power. Every time we blink or smile or yawn, we're using up energy. Energy that comes from the food we eat. Our bodies have a complex system to break it down and turn it into the energy that we need for every day life. But what if our bodies couldn't break down an essential energy source? Brenna: Today we're going to talk about, the very-long-chain acyl-CoA dehydrogenase deficiency, or more commonly known at VLCAD. For individuals with VLCAD, the enzyme required to break down long-chain fats is not working properly. This means that their bodies are not able to utilize the energy source. Today, we're going to explore this condition and what it means for day to day life. Brenna: For families and individuals facing a new diagnosis, you likely have more questions than answers. That's why we're here. We are Disease Connection, and 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 and where are the people who've been through this before?" You'll find those answers here. From doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families. They're all with your reach, and we're here to connect you. This is Rare Disease Connection. Brenna: Hey, everyone, this is Brenna, cohost over at Disease Connection. Today I'm going to be bringing you conversations with experts in VLCAD. Before we get started, you should know that this podcast is just the beginning. We've taken the information from this episode 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/VLCAD. That's raredisease.com/VLCAD. So, let's get started. Brenna: Our first guest today is Erika Beckman, a genetic counselor in Seattle, Washington. Thanks for joining us today. I was hoping you could start off just by telling us a little bit about yourself. Erika Beckman: Yeah, absolutely. So my name is Erika Beckman, I am a genetic counselor currently practicing in Seattle, Washington. I received my master's degree in human genetics and genetic counseling from Stanford University in 2019. After graduation, I took a job as a genetic counselor here at Seattle Children's Hospital and I've worked here for about a year now. Erika Beckman: Specifically, I work in the biochemical genetics clinic, so I work alongside a team of biochemical geneticists, a second genetic counselor, dieticians, nurses, and a social worker. Not a lot of people know what biochemical genetics is, but biochemical genetics is essentially a subspecialty of genetics that involves diagnosing and treating metabolic diseases. Metabolic diseases are problems with how the body makes, breaks down, or uses molecules in our body. For example, proteins, fats, or carbohydrates. So these conditions are all causes by genes that are not working properly and cannot make the enzymes that the body needs to make these processes occur. So our team helps to diagnose, monitor, and manage these diseases. Erika Beckman: VLCAD deficiency is a biochemical genetic disorder, so we see many individuals with this condition in our clinic. We see patients both inpatient and outpatient. We typically see individuals with this diagnosis ranging from newborn babies to adults. We have all of these individuals on an annual basis to help manage their disease. Brenna: So speaking from your experience as this rare subspecialty as a biochemical genetic counselor, when you hear VLCAD, what immediately comes to mind for you? Erika Beckman: That's a great question. I would say the first thing that comes to mind is the value of newborn screening. So all babies born in the United States are screened for certain medical conditions shortly after birth. The medical conditions screened for vary by state, but each state must screen for a minimum set of conditions. The conditions included on a newborn screening are all conditions that are important for early detection in order to start treatment, and identifying these conditions soon after birth can help prevent serious health problems and save many babies lives. VLCAD deficiency is one of the conditions that's included on the newborn screening program. Erika Beckman: Individuals with VLCAD deficiency can present in many different ways and with different severity, but the most severe form of the condition can present in the first few months to year of life with early onset cardiac and multi organ failure if not treated. That was a driving motivation for it to be added to newborn screening programs. Erika Beckman: Before VLCAD was on newborn screening, many babies with the early onset form would present with severe symptoms and unfortunately, often pass away within their first few months to year of life. In fact, VLCAD is one of the causes we think of when a baby passes away from SIDS or Sudden Infant Death Syndrome. However, with the early detection through newborn screening and initiation of early treatment, many of these serious complications can be treated or avoided, which has allowed many more children to grow up and lead normal lives. Erika Beckman: So when I think of VLCAD, I guess the first thing I think about is all those children and families that have had a chance to grow up together and the time that they might not have had without it being on newborn screening. Brenna: Yeah, I think speaking as a genetic counselor myself, newborn screening is always something that I really value because sometimes we have so many conditions that we don't know maybe until it's too late or there's not so much we can do, but these metabolic conditions for a lot of them, there are treatments or managements. So that's really awesome. Erika Beckman: Yeah, absolutely. Brenna: So, taking a moment to look at the basics of this condition. What's actually occurring at a genetic level that's causing this condition? Erika Beckman: Yeah, so VLCAD deficiency belongs to a larger group of metabolic conditions called Fatty Acid Oxidation Disorders. The Fatty Acid Oxidation process is the process in our bodies that breaks down fats and converts them to energy. So Fatty Acid Oxidation Disorders are conditions that affect how the body breaks down fats. Erika Beckman: If you think about normally when people eat food, our body first uses the carbohydrates in that food for energy. When the body runs out of carbohydrates to use for energy, say when you're exercising or you haven't eaten in a while or you're sick and you're not taking in as much food in general, then your body switches to use fats for energy instead. But when someone has a Fatty Acid Oxidation Disorder, they're not able to use fats for energy, which can lead to serious symptoms, especially during times when your body is in a period of stress and needs that energy. Erika Beckman: So fats or fatty acids are built like chains, and they come in many different lengths. They're classified as either short, medium, long, or very long. An individual who has VLCAD is not able to break down very-long-chain fatty acids to use them for energy. Erika Beckman: The gene associated with VLCAD is called ACADVL, and the ACADVL gene provides instructions for making an enzyme in the body called very-long-chain acyl-CoA dehydrogenase, which is why the condition is called what it is and why we refer to it as VLCAD for short, because it's a mouthful. But the job of this enzyme is to break down those very-long-chain fatty acids in the fatty acid oxidation process. So when someone has a variant or a spelling mistake in that gene, then the enzyme is not made properly and very-long-chain fatty acids are not able to be broken down for energy. Brenna: That makes sense, it's all this one big process. Our bodies are just such a vessel for just taking in food and creating energy to get us to where we need to be. It's such a complicated process at every step, with every single enzyme can sometimes go wrong. So I think that really helps clarify what's going on. Erika Beckman: Yeah, I'm glad. We often don't think about how many of those steps and processes are happening in our body when we eat. Brenna: So knowing that this is a genetic condition, is this something that's inherited? Can this be passed down from a parent? Erika Beckman: Yes, VLCAD deficiency is an inherited condition. VLCAD deficiency is what we call an autosomal recessive condition. We all have two copies of that ACADVL gene. We inherit one of those copies from our mom and one of those copies from our dad. In an autosomal recessive condition, it means that in order to have that condition, an individual must have a variant, sometimes called a mutation, but essentially a spelling mistake, in both copies of that ACADVL gene. Erika Beckman: So you can imagine that if we inherit our copies of that gene from our parents, and an affected individual has a variant in both copies. Then most likely, one of those variants came from their mom and one of those variants came from their dad. There is always the possibility that one or both of those variants are new in an individual, but most of the time they're inherited from their parents. What that means for those parents, is that the person, the parent who has one variant in one copy of ACADVL, as well as a normal copy of that gene, they're considered a carrier of VLCAD deficiency. Typically, a carrier does not show symptoms of VLCAD deficient because that normal copy of the gene is still working well enough to not have symptoms of the condition. Erika Beckman: So, pregnancies between two individuals who are carriers of VLCAD deficiency have a 25% chance to have an unaffected child. A 50% chance to have a child that's also a carrier of the condition. Then a 25% chance to have a child that is affected with VLCAD deficiency. It's very normal to be a carrier of a genetic condition. It's estimated that every person is a carrier of a few genetic conditions, specifically autosomal recessive conditions. We might just not know that until we have a child with someone who is also a carrier of the same condition. Erika Beckman: Then in the future when an individual who is affected with VLCAD deficiency goes on to have their own children, then they will have to pass on one of those variants that they have to every child, but whether or not that child is also affected, would depend on whether or not that individual's partner has VLCAD or is a carrier. They could have genetic testing to figure that out. Brenna: So after we've learned a little bit about the genetics and what's going on, going back to a clinic and what someone might present as. What might make a physician or a geneticist suspicious that someone might have VLCAD? Erika Beckman: So because VLCAD is on newborn screening, the most common way that we identify affected individuals nowadays is when they have a positive newborn screen. Often times that comes back before a patient ever has symptoms of the condition, and if a baby has a positive newborn screen for VLCAD, then they're typically referred for an appointment at a center for metabolic diseases, like the clinic that I work in, for further evaluation to confirm or rule out a diagnosis. Erika Beckman: Sometimes, if a baby has the severe early onset form of VLCAD, that baby might start having symptoms before newborn screening results are back. Those could include things like tiredness or sleepiness, behavior changes, and irritability, low muscle tone or hypertonia, poor appetite, vomiting, diarrhea, hypoglycemia, which is low blood sugars, and cardiac symptoms, or cardiac failure. If we see an individual with those symptoms admitted in the hospital or outpatient, then we would likely recommend a workup for a Fatty Acid Oxidation Disorder. Erika Beckman: Additionally, even though most children are picked up on newborn screening nowadays, there could be children who were one, missed on newborn screening, or two, didn't get newborn screening because for example, they were born in another country that doesn't screen for this condition. Or, an individual might present with symptoms who had newborn screening before VLCAD was added. So for example in Washington, VLCAD was added to our newborn screening program in 2008. So we certainly could see patients that were born before 2008 presenting with symptoms. Erika Beckman: There are different forms of VLCAD and depending on the type that individual has, they might present with different symptoms, but they typically could include things like hypoglycemia or low blood sugar, hepatomegaly, which is an enlarged liver, or rhabdomyolysis, which is breakdown of damaged skeletal muscle. They could present with these symptoms either during an illness or maybe after a period of fasting or while exercising because like we talked about, that's often when the body runs out of carbohydrates and has to turn to fats for energy, but they're not able to process them. Brenna: So let's say someone was not picked up on newborn screening, for any of the reasons that you listed. They're presenting with symptoms. How does someone actually receive a diagnosis? What testing is needed? Erika Beckman: So there's really two main categories of testing to work out a diagnosis. One of those is biochemical testing. So if a provider is suspicious of VLCAD or a Fatty Acid Oxidation Disorder, they would likely recommend obtaining biochemical screening tests to look for abnormal values in the blood. Erika Beckman: The primary biochemical screening test that's recommended for VLCAD is called an acylcarnitine profile, and that essentially is a test that looks at levels of fatty acids of all chain lengths in the blood, and if someone has VLCAD, then you would expect to see an elevation in their longer chain fatty acids because they're not able to break them down. If you think about how the fatty acids are numbered based on how many carbons they have, the elevations you typically see in VLCAD are the C14 fatty acids. C14:1 is the metabolite that's used to screen babies on newborn screening, and if that's inconclusive, then there are some additional biochemical tests that can be done. For example, looking at how well the VLCAD enzyme itself actually is working and how efficient it is at breaking down very-long-chain fatty acids. Erika Beckman: But then the other category of testing is genetic testing. A provider would likely recommend that either in conjunction with or after those biochemical screening tests come back. This is typically done with a blood sample and it's sent to a laboratory where they read through the individual letters of the ACADVL chain that is associated with VLCAD. If someone has VLCAD, since it's an autosomal recessive condition, we would expect to find two pathogenic or disease causing variants in that gene, which would confirm a diagnosis of VLCAD. Brenna: So from my understanding, there's multiple subtypes to VLCAD. Can you break down those subtypes for us a little bit and maybe what they might mean for patients? Erika Beckman: Yeah, you're absolutely right. We've alluded to this a little bit throughout the interview. The three subtypes are delineated based on the age of onset, as well as the types of symptoms that an individual develops. The first subtype is the early onset severe form. So this typically presents in infants in the first few months of life to year of life with cardiac finding. So that could include cardiomyopathy, paracardial fusion, which is fluid around the heart, and arrhythmias, which are abnormal heart rhythms. Infants typically have hypotonia, or low muscle tone, hepatomegaly, the enlarged liver, and hypoglycemia, which are low blood sugars. The cardiac finding especially can be life threatening, and is therefore important to diagnose someone early so that treatment can be started as soon as possible. Erika Beckman: The second subtype of VLCAD is called the hepatic or hypo ketotic hypoglycemia from of the condition. That typically presents in early child with hypoglycemia and hepatomegaly, but without the cardiac findings. That being said, hypoglycemia can also be dangerous if not treated, so it's still important to identify these individuals and start treatment. Erika Beckman: Then the third form of, or subtype of the condition is called the Later Onset Episodic Myopathic form of VLCAD deficiency. This typically presents with intermittent rhabdomyolysis. Rhabdomyolysis like I mentioned earlier, is the breakdown of damaged or injured skeletal muscle. That releases toxic chemicals called myoglobin into the blood, which can be dangerous to the kidneys. These episodes are often provoked by exercise. Erika Beckman: There are actually strong correlations between the type of genetic variants that someone has in their ACADVL gene and the form of disease that they'll develop. That is dependent on how much that gene is able to make any residual enzyme to work in the body. Brenna: So once someone has gone through all of this testing, we've had biochemical testing, we've had genetic testing, and they've got their diagnosis. What assessment and monitoring will these patients need? Erika Beckman: That's going to depend on the subtype of VLCAD that individual has, as well as how severe their symptoms are, but regardless of the type, if an individual's diagnosed with VLCAD, they will likely be followed by a biochemical or metabolic genetics clinic for life. That usually becomes a medical home to help coordinate treatment and other specialists. Erika Beckman: First off, the provider would likely recommend essentially, surveillance type workup. So lab work to assess for any evidence of rhabdomyolysis for the breakdown of muscle tissue, as well as to ensure that the liver is working properly. Also, because of the risk for cardiac findings, they would likely recommend an echocardiogram, which is an ultrasound of the heart, and an EKG, which looks at the rhythms of the heart. Erika Beckman: But the primary treatment for VLCAD deficiency is dietary. So a metabolic dietician will likely be part of the care team for an individual with VLCAD. Individuals with the severe form of VLCAD are typically placed on a low fat diet but supplemented with what we call medium-chain triglycerides, or MCT, because individuals with VLCAD cannot break down longer chain fats. There is actually a different enzyme used to break down medium-chain fat. So the idea is to prioritize giving the body fats that they can break down for energy. Erika Beckman: Especially when younger, it'll be recommended that individuals with VLCAD don't fast or go without food for a long amount of time because that's when your body switches to using fats for energy and they can't do that properly. If an individual with VLCAD gets sick with a cold or the flu, where someone typically eats less, the care team will likely recommend what we call a sick day diet. That essentially means that they're taking in more foods that they can break down, so more carbohydrates than fat, to help compensate for the lack of calories they're taking in overall. Erika Beckman: There are more experimental treatments for really severe cases, including a drug called Triheptanoin, that's essentially a medium-chain oil that has had really promising impacts on severely affected children, primarily improving the cardiomyopathy, but not so much the skeletal muscle. They actually applied for FDA approval of Triheptanoin this summer. Brenna: So it's nice to know that this seems to be definitely something that can be managed with a care team, with diet, with avoidance of fasting. So there's definitely things you can do, and now there's even more treatment on the way. So that's really hopeful for patients who have VLCAD. Erika Beckman: I agree, it's a very promising time in research and treatments for this condition. Brenna: So building off of your management recommendations, is there anything specific that someone can do or something that someone can avoid to help manage VLCAD? Erika Beckman: Yeah, so the goal for managing VLCAD is really to avoid, "triggers." So that includes avoiding fasting, avoiding a high fat diet. So for example, the ketogenic diet or a low carbohydrate diet should be avoided in individuals with VLCAD. Additionally, some individuals may have restrictions on exercise or certain precautions put in place so that they can exercise safely. For example, maybe taking more MCT or medium-chain fats before exercise. Erika Beckman: An individual with VLCAD will typically be provided with an emergency protocol letter by their healthcare team, so that if they do get sick or do have to go to the emergency room, either at their local hospital or somewhere else, then they will have a letter to provide to the doctors that explains their condition and provides recommendations on precautions that should be taken. Often that includes getting an IV dextrose or sugar, and no fats at all, to help provide the body with more nutrients that they're able to process for energy. Erika Beckman: The other thing I wanted to mention is pregnancy when you have VLCAD. For individuals that are diagnosed with VLCAD, it is possible for them to carry a pregnancy and have children. Often times symptoms actually may improve during pregnancy, however, the actual labor and post partum period are stressful events on the body and do put them on at an increased risk for, especially rhabdomyolysis. So it is important to have a management plan for labor and delivery to make sure that mom is safe during that time. Brenna: So I want to thank you again, Erika, for taking time with us today. If you had one piece of advice about VLCAD for someone who's either just been diagnosed or maybe has a loved one who's diagnosed or affected, what would that be? Erika Beckman: Yeah, so I think my biggest piece of advice would be to say that they're not alone. So whether you're a new parent learning this about your baby or an adult learning this for the first time about their self, it's undoubtedly scary to receive a new diagnosis of a genetic condition. It's important to know that there are others out there that are also living with this diagnosis, and that there are treatments available to help individuals with VLCAD live long, healthy lives. There, like we mentioned, is a lot of active research going into VLCAD deficiency to improve upon current treatments. There are great resources and support organizations out there, such as the Fatty Acid Oxidation Disorder's Family Support Group where families can go to interact with others who also live with these conditions. Erika Beckman: Lastly, your care team is here to answer any questions and communicate with you to make sure you that you're receiving the best care you possibly can. Brenna: Thanks, Erika. If you have just received a diagnosis or if you want to learn more about VLCAD, a genetic counselor can help you. If you or a family member have questions, I recommend looking at nsgc.com, to find a genetic counselor near you. Brenna: Our next guest is Dr. Dan Sharer, the Director of the Clinical Biochemical Genetics Laboratory at UAB. Thanks for spending time with us today. So why don't you just start off by introducing us to you? Dan Sharer: So, my name is Dan Sharer, I am a Professor of Genetics and I'm the Director of the Clinical Biochemical Genetics Laboratory at the University of Alabama at Birmingham, better known as UAB. I trained at Emery University in Atlanta a long time ago, and I am boarded by the American Board of Medical Genetics in clinical biochemical genetics. Dan Sharer: I have a little bit of experience with VLCAD deficiency, mainly from the fact that my laboratory performs testing that can help diagnose that particular condition. We also act as the followup training program or follow up testing program, I should say, for the Alabama newborn screening program. Brenna: So, thinking about all of that experience, when you hear VLCAD, what immediately comes to mind for you? Dan Sharer: So, this is a rare but serious genetic condition, in which fatty acids cannot be utilized for energy. So because of that when a patient presents with an increased risk for this condition, either due to the fact that they're presenting with clinical symptoms, or due to abnormal newborn screening results. It's imperative for us to complete testing and communicate those results as quickly as possible back to the physician for the patient, in order to allow for the best possible outcome for that patient. Brenna: So, you state that this is a rare genetic disorder. Exactly how common is this? Is there certain populations or areas of the world where you might see it more frequently? Dan Sharer: So VLCAD, and by the way, that's an acronym for the metabolic enzyme that's not working in that particular disease, which has the very long and unwieldy name, very-long-chain acyl-CoA dehydrogenase deficiency, or VLCAD. So this is a rare disorder, it has a published incidence in the United States anywhere from one in 30,000 to one in 100,000 births, depending on what the source is. I'm not aware of any populations around the world where that prevalence is significantly outside of that particular range. Brenna: So taking a step back and looking at VLCAD, we've talked about it's a genetic condition. What's actually going on, on a biological level that causes the signs and symptoms that you see in individuals with this disorder? Dan Sharer: So yeah, that's a good question. Something I could probably talk about all day long, which wouldn't be very exciting, but. So this is a disorder of fatty acid utilization, fatty acid oxidation. So fatty acids are fats and these are an extremely important energy source for the body, and particularly for the heart. 70% to 80% of the energy that you use to keep your heart beating normally at all times is from breaking down fats. Dan Sharer: So fatty acids are metabolized by a whole group of different enzymes, many of which are found in mitochondria and other places, and VLCAD is one of these enzymes. So when you have VLCAD deficiency, and that means the baby or the patient has inherited two dysfunctional alleles of the VLCAD gene, so it has no source or normal VLCAD enzyme function. So that results in an inability to metabolize those fats for energy. That results then in an energy deficient state, not surprisingly. That's usually characterized by what we call hypoglycemia or low blood sugar. Blood sugar, glucose, is one of the common currencies of energy in the body. That gets used up pretty quickly and if there's no fat to fill in behind that, that creates that energy deficient state. Dan Sharer: Because fats are so important for the heart, patients with severe VLCAD can then have what we call cardiomyopathy, which is heart disease. That can be fatal in severe cases. These patients often also have liver disease, which is due to secondary toxicity of fatty acids. Later onset or milder forms can have skeletal muscle weakness as well. Brenna: So now that we've gone through what this looks like, in terms of presentations of how a patient might present, let's think about how this is caught and how it's diagnosed. So you've mentioned that UAB has the followup testing site for the Alabama newborn screening. From my understanding, this is a condition that can be caught on that newborn screening. Can you walk us through what happens after that baby's heel is pricked in the hospital? Dan Sharer: Yeah, so this is a fascinating process, it takes place in all 50 states and in countries around the world. So once the baby's heel is pricked, they collect a little bit of blood on a piece of filter paper. That is mailed to the newborn screening lab, wherever that may be. In the case of Alabama, we have a lab down in Montgomery that does the newborn screening. If they find that the patient has an abnormal result that is suggestive of VLCAD deficiency, again, it's important to remember this is a screening test, not a diagnostic test. If that abnormal result is found, then there's a very rapid process set into motion where the physician and the state newborn screening followup coordinator, those individuals are contacted because of that result. Dan Sharer: Followup testing is coordinated, and again, that's done through my laboratory here in Alabama, if our results are consistent with the newborn screening results, then ultimately, the patient receives a final diagnosis of the VLCAD deficiency. Then the patient is put on a specific treatment regimen, which in this case usually involves special dietary restrictions. As long as all that works properly, it happens very quickly. It happens before the patient ever develops any symptoms, and so the outcomes there are greatly improved as a result. Brenna: So you mentioned it's a screening test, it's not diagnostic, but how accurate is that screen? Do you get a lot of false positives or false negatives? Dan Sharer: Well, so again yeah, it's a screening test. How I like to describe that is, it's basically designed to look at a large population of individuals with no prior information about what's going on. So it essentially differentiates those who probably have the disease from those who probably do not have the disease. So it's pretty good at that, but it's still just a screen. So that means that occasionally, you can have a false positive result, meaning you get an abnormal test result but the patient doesn't really have the disease. So this can occur if the baby is a carrier, so they have one mutated VLCAD gene, they don't actually have the disease, but based on the test result we get back, it looks like they may have the disease. So additional testing has to be done. Dan Sharer: Also, if a baby is sick or malnourished and has something called ketone bodies at relatively high levels in their blood stream, then that can also look like they may have VLCAD deficiency. But again, additional testing will clarify the difference between true VLCAD and a ketotic state. Dan Sharer: Then you can also have false negative results, where you get a normal test result but the patient really does have the disease. So you've missed the disease there. So this can occur if the baby is particularly well nourished when the sample was collected, or has had a recent glucose infusion, that can mask the results of the screen. This is especially true for milder forms of VLCAD, and VLCAD is known for being one of these diseases where you can potentially miss it because the patient is actually physiologically well. So in this case, the diagnosis may be delayed until the patient becomes symptomatic, in which case the newborn screening part hasn't really worked as well as we would like. Brenna: So in that last part you alluded to a milder form. I know that there's different forms of VLCAD. Are you able to differentiate those types on the biochemical testing that you do, either in the screening or in that followup testing? Dan Sharer: Yeah, so VLCAD is conveniently described as having two or even three different forms. So there's the severe early onset form, which usually presents earlier in life, first few months of life. That's the form that we're really trying to catch because that's the one where you can actually have relatively high mortality due to the heart condition that's associated with that. There's also a moderate hepatic form, a form that has liver involvement, and that presents also with that low blood sugar, and they also have enlarged liver as well. That usually is seen in early childhood, a little bit older. Dan Sharer: Then there's a late onset, what we call a myopathic form, that presents with exercise intolerance and muscle pain. This is often seen during adolescence and we often see a couple of cases of this each year in the late summer when summer football practice has actually started. We get a couple of patients who come along who have just gone through a rigorous practice and they have this severe muscle pain. They actually have something called myoglobinuria, where they actually have products of muscle tissue breakdown in their blood and in their urine. Dan Sharer: So in terms of testing, so we're mainly looking at fatty acid intermediate, something called acylcarnitines, or doing enzyme testing. That's really what the biochemical testing is all about. Now, all these approaches can something differentiate between say, the severe and the mild form of VLCAD. The results are often ambiguous, the results often overlap to the point where we can't clearly say that it's one or the other. Now the same can be said in terms of being somewhat ambiguous, for certain types of molecular results as well. So I usually tell trainees, patients, and their families, the best approach is really a multidisciplinary approach where you're combining the different laboratory test results and any clinical information you have about the patient, in order to get the most clear, the most precise diagnosis made. Brenna: So after someone has that diagnosis, they've gone through all this testing, they've been looked at by physicians. Who should be a part of their care team? Dan Sharer: So just in a general sense, patients with inborn errors of metabolism like VLCAD, usually have a very comprehensive care team working with them. This includes clinical geneticists, and particularly for a rare disease like this, someone who is trained in medical biochemical genetics, has a real leg up in terms of dealing with this condition. Certainly, genetic counselors who are trained to deal with that interface between the clinicians and the parents and the family. Dieticians to manage the dietary treatment of the patient. Pediatricians, whoever's involved with the patient's care, based on their needs as they grow and develop. All those individuals have to be working together to optimize the outcome in terms of these patients. But we know enough now about these individuals that if we have that early diagnosis, get them on treatment and monitor their treatment, these patients can do extremely well. Brenna: I just want to thank you again, Dr. Sharer, for spending time with us today. You've got a ton of experience as a laboratory director and really were able to walk us through a lot of the nuances. So, in closing before we say good bye to you and let you go, is there anything that you'd like to leave the listeners with about VLCAD, a final message? Dan Sharer: So in general, these are really rare disorders, but they do pop up now and then. They're potentially very serious, but the great thing about metabolic disorders is that many of them can be affectively diagnosed and treated if they're picked up early and the treatment begins early. This is where newborn screening is really a wonderful public health program for picking up these rare disorders and making them manageable. We can cure them yet but we can certainly treat them effectively. So I think that's the main thing that I want to get across. Brenna: Thank you, Dr. Sharer, for taking the time to walk us through what happens in a biochemical laboratory and giving us some insight into testing. Brenna: Our final guest is Deb Lee Gould, the Co-founder and Director of the FOD Family Support Group. Deb started this group after a personal experience with a Fatty Acid Oxidation Disorder. Thank you for sharing your time and story with us today. So, why don't you start out by introducing yourself? Deb Lee Gould: Okay, my name is Deb Lee Gould, and I am the Co-founder and Director of the FOD Family Support Group. FOD stands for Fatty Acid Oxidation Disorders, which are rare genetic, metabolic disorders. I run all of the support forums for this group, I've been doing this since 1991. All the Facebook groups, Google groups, put on conferences and things. So just the overall worldwide support for families living with these disorders, as well as we're open to professionals that actually work with our families. Brenna: So speaking from all of that experience, today we're talking about a specific Fatty Acid Oxidation Disorder called VLCAD, but when you think of fatty acid oxidations as whole, what immediately comes to mind for you? Deb Lee Gould: Well first off, they're pretty much invisible disorders. You can't look at someone and say, "Oh, they have an FOD," or, "There is a challenge that this child or adult is living with." The main thing that I think of is that they are highly treatable disorders if you know you have one. If for some reason you don't know you have it, and often times they are picked up with newborn screening today, but as in our case as you know, we didn't have newborn screening when our first child was born. We didn't know she had one of the FODs. So we do have fatalities in our membership, but overall all of the 13 or 14 various FODs are very treatable if you know you have it. Brenna: So you touched on a little bit of your personal connection to fatty acid oxidations. Can you tell me a little bit more about your family? Deb Lee Gould: Right, back in... well, I always talk about it in a way, my previous and my life now. So in my previous life, my husband and I, we've been married almost 41 years and we started our careers. He is a sports psychologist and I taught physical education at the time, K through four. We made the decision to start our family and in 1983, we were blessed with our first child, Kristin, our daughter, was born in October. You look at her and she's developing normally and active and everything. Deb Lee Gould: Then fast forward to about 21 months, she woke up one morning and projectile vomited. Dan was out of town, he traveled the world with his work, so I called the emergency line, the nurse advisory. It was a Sunday, and she said, "The flu is going around, let her sleep." So I let her sleep and I'm keeping an eye on her and throughout the day I called the nurse two or three other times. The fourth time I called her, because I was concerned because she wasn't waking up and she needed to eat. She stopped breathing as I'm on the phone with the nurse advisory or the advisory nurse. Deb Lee Gould: So they called 911 for us, Dan had gotten home from his trip in the meantime. We started CPR on her and got her heart going again. Got her to the hospital and within two hours, we turned the machines off. They could not save her. They had no clue what it was and back in the '80s, the Tylenol scare was going on, we thought, well maybe she got into something that. She didn't, we didn't give her anything like that. Upon autopsy, they determined, they said it looked like Reye's syndrome, fatty liver, fatty heart, high ammonia levels in her brain. We felt in our hearts that that wasn't it. Deb Lee Gould: So we were in Champagne, Illinois at the time and looked through medical books and couldn't find anything. We were fortunate when we made our decision to continue our family, I was pregnant with Kevin and we were given an article about MCAD and how it mimics Reye's Syndrome. We said this next child will be tested, and our doctor said, "No, that's rare. It couldn't be that." We insisted that Kevin was going to be tested. When he was born, we had blood sent to Duke and within 24 hours we got a call saying Kevin has MCAD, which is the most common FOD. Fortunately, they had saved some liver tissue from Kristin's autopsy, so a year later she was diagnosed with MCAD as well. So she was the first documented post mortem diagnosis and Kevin at the time was the youngest infant to be diagnosed with it. Our third child Brian is a carrier. So he's not directly affected. Deb Lee Gould: So we were thrust into the world of metabolics and a few years after Kevin was born, we talked with Dr. Rowe, who was the doctor that diagnosed him and also developed the newborn screen test with two other doctors for FODs. We were talking and we were saying we feel so alone in this journey. We just decided well, why don't we create a support group, so we did that. We started with 10 families and they were mostly MCAD families because that was really the only one that we knew about back then. So we started with 10 families and this is in 1991. In 1995, we expanded to include all of the FODs. So now we probably have about 5,000 or 6,000 families around the world that are living with these disorders. So that's how we came to starting the group and offering support. There's no charge for families at all to join our group. We just want to offer support. Deb Lee Gould: We had found that after Kristin's death, we found a support group called Compassionate Friends. We felt really comforted by that, and that was a free group. So we wanted to be able to offer our support for free so families wouldn't have to feel so alone. We actually use that phrase that you're hearing around the world now, "We're all in this together." That was our group's motto or mission statement. Yes, we are all in this together and you are not alone. So, we really focus on that in our advocacy for families. Brenna: Yeah, I think that's an amazing story and one that we hear from a number of support groups that it's blossomed out of a personal connection or tragedy, that's really been turned into something quite inspirational for so many families. Brenna: What has it been like for you to start with just 10 families, that how did you find those 10 families? Then to see now with 5,000 individuals. Deb Lee Gould: Right, well with HIPAA and all of that, we had to go through Dr. Rowe. So he actually sent out letter for us. We wrote up a letter saying that we'd like to form this group. So he sent it out to all of the families that he was working with and we had 10 responses. So that's how we started. The internet really wasn't up and running, so we started with a text, just a printed newsletter, so we mailed that out. Then we started getting bigger and bigger and it was getting costly to do that, so and then the internet came on. We started with a text website, no graphics, just text. Deb Lee Gould: Then one of our family members also had an MCAD child that didn't know she had MCAD and she had died as well. So she is our webmaster and has created this wonderful website for us. We just keep evolving with that and adding more information. We've got all of our information from 1991 on, on our website. Deb Lee Gould: So, it's been wonderful. To be able to meet families now face to face, either FaceTime or on Zoom, or we used to run large conferences and now we're going more toward regional meetups, but to be able to actually meet these families and they can connect with us and find that support that they may not be getting locally or even within their own families. Their families think, oh, they may outgrow this. This is not something to outgrow, these are genetic disorders. So they know that when they come to our group, that they will be seen and heard and understood. That's anyone that comes to our group. We are an all-inclusive group. Brenna: Absolutely, I think that's just such a wonderful message because I think you hit the nail right on the head that unless you're personally facing either with yourself or a family member with one of these genetic conditions, it's really hard to understand what it's like if you're not in it. Deb Lee Gould: That's right, absolutely. Brenna: So, you offered free grief counseling for parents and children. You've got the opportunity to meet so many families with Fatty Acid Oxidation Disorders. In your experience or your opinion, what seems to be the most challenging aspect of these conditions? What seems to help families the most? Deb Lee Gould: Well, I would say one of the most challenging, there's many, but one of the most is actually finding metabolic specialists that actually understand and know Fatty Oxidation Disorders. We've got families that cross several states just to see a specialist. Families in the rural area, families in India or China, Australia. They often don't have enough metabolic specialists to be able to treat their child or themselves. We are getting more and more adults being diagnosed with these disorders now. They were once passed off as, oh, it's all in your head or it's febrile myalgia or chronic fatigue. They are being diagnosed as well, so they're also finding it difficult to find the support with their families or at work, to fully understand them. So that's what we try to provide for them, is that support. Brenna: Absolutely, so you've spoken so much of all the great thing that your organization does. Is there any events or initiatives that you'd like to highlight? Anything that's coming up? Deb Lee Gould: Yeah, we as a group have designated July as FOD awareness month. It's not a national thing or anything but we like to talk about our stories and we try to encourage our families to be proactive and to share their stories with their other family members, their friends, their online walls on Facebook, if they do a blog, so share their stories there. As well as their other medical professionals, so that they know this is going on within their family. So, just to spread the word. Deb Lee Gould: You see I'm wearing an FOD polo shirt, we offer online our awareness items, lapel pins and baseball hats and things like that. I wear mine every day and I get people that ask me, "What does FOD stand for?" You can share your story from there. Deb Lee Gould: So we've got July coming up and so we try to promote FODs. In October, we hope to be part of the Rare New England Conference. That's another non-profit that deals with rare disorders, a wide variety of rare disorders. They have invited us to do our regional meetup within their conference. So we'll have a few breakout sessions with our family, since we're downsizing from big conferences, but with everything going on in the world today, we may be going virtual with that. So that'll be our nother event. Those are the types of programs that we have. Deb Lee Gould: Our main service in our program is the support, online, via phone. I call families and I try to Skype or Zoom families across the globe especially new families so that they don't feel so alone and frightened. You get a diagnosis like this and often times you think your child's going to immediately die, which we felt when Kevin was born. We thought we were going to have another death. So until you get more knowledge and you learn that there's research out there and there is treatment that can be very effective, and you're bolstered up by support, you are able to make it through. Your child and adult can have a healthy and active life. Brenna: So what is the best way for families who are interested to get connected with you guys? Deb Lee Gould: Well, we have a website for the FOD group and that's fodsupport.org. My email is firstname.lastname@example.org. I also have a grief consulting site for families, FOD families and other. That is bereavedparent.com or .org. The email is email@example.com. Brenna: So, thank you again, so much for spending time with us today and sharing your story and your initiative with the FOD Foundation. In closing, what's one message that you would like to leave our listeners with about Fatty Acid Oxidation Disorders? Deb Lee Gould: Okay, the main message I'd like to leave is that when new parents are asked to sign that consent for newborn screening, please sign it. While you're waiting for results, supplement your child because we have had some challenges with babies until when they get their results. They could come seven days and you could already have a metabolic crisis. So you want to supplement in the meantime because by signing that form and having the newborn screen, you could just be saving your child's life. Brenna: Thank you, Deb, for your support of others with Fatty Acid Oxidation Disorders. Your organization provides so many resources and opportunities for families to connect. If you are interested in getting involved, you can go to their website at www.fodsupport.org, to learn more. Brenna: Thank you all so much for joining us today as we unpacked VLCAD. Thank you for all of the experts who took the time to share their experiences. This episode, it's just the beginning. We've taken all of today's information and included it in a free downloadable guide. You can get your free copy by going to raredisease.com/VLCAD. We would love to connect with you, if you need to talk to someone, we're standing by. Go to raredisease.com/help, we're waiting for you. Brenna: Rare Disease Connection is a production of Aspect Health and raredisease.com. Thanks for joining us.