Isovaleric Acidemia: Stephen and Caroline's Stories
Jana and her 13 year old son Stephen and 8 year old daughter Caroline visited FDAs Office of Orphan Products Development (OOPD), and Jana talked about their experiences with isovaleric acidemia (IVA). Stephen was diagnosed with IVA when he was 3-½ years old and Caroline was diagnosed before she was born (prenatally) and received early treatment: two children with the same disease but different outcomes.
IVA is a rare metabolic disorder in which the body has inadequate levels of an enzyme that breaks down the amino acid leucine, which is a part of proteins in foods that we eat. As a result there is a build up of isovaleric acid which may become harmful to the body, and in individuals with acute illness leads to a characteristic smell of sweaty socks. IVA causes episodes of illness called metabolic crisis. It is usually diagnosed within the first two weeks of life with poor feeding, vomiting, seizures, decreased level of consciousness, and elevated blood levels of ammonia which can lead to a coma and can be life-threatening. However, these signs and symptoms may come and go during childhood, triggered by such things as infections or by eating an increased amount of protein-rich food, which can lead to failure to thrive and developmental delays and potentially to metabolic crisis. Some people have no symptoms or very mild symptoms and are only found to be affected after a sibling is diagnosed. IVA is estimated to affect at least 1 in 250,000 people in the United States.
Jana tells FDA staff about how Stephen was first diagnosed with isovaleric acidemia (IVA) when he was 3-½ years old. Although doctors recognized that Stephen was in a metabolic crisis and were able to diagnose him with IVA, brain swelling had already occurred due to elevations in isovaleric acid. Stephen was in the hospital for four weeks and six weeks at a rehabilitation center. Today, Stephen is in a wheelchair, isn’t able to speak, continues to have seizures, and needs to be fed through a gastrostomy tube.
Jana talks about how she learned that she was pregnant with Caroline within the first year after Stephen’s diagnosis with IVA. Mutations in the isovaleryl-CoA dehydrogenase (IVD) gene cause IVA, which is inherited in an autosomal recessive manner, meaning both copies of the gene have mutations and thus the parents are usually carriers. Each child born to parents who are carriers has a 25% risk to have IVA. Prenatal testing was performed, and it was determined that Caroline also had IVA. Caroline’s delivery was induced a week early so that doctors could be ready to treat her immediately at birth.
Dr. Cote talks to Caroline about what she eats. Jana explains the different aspects of therapy for IVA, one of which is the use of a medical food as part of their diet. The term "medical foods" does not pertain to all foods fed to sick patients. Medical foods are foods that are specially formulated and processed (as opposed to a naturally occurring foodstuff used in a natural state) for the patient who is seriously ill or who requires the product as a major treatment modality. In general, to be considered a medical food, a product must, at a minimum, meet the following criteria: the product must be a food for oral or tube feeding; the product must be labeled for the dietary management of a specific medical disorder, disease, or condition for which there are distinctive nutritional requirements; and the product must be intended to be used under medical supervision. Jana also explains that medical foods can be expensive and may not be paid for by insurance companies.
Jana talks about how in her role as an advocate for her children and others she would like to raise awareness about IVA and the availability of newborn screening for metabolic disorders.
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