Isovaleric Acidemia

ISOVALERIC ACIDEMIA

What is Isovaleric Acidemia?

Isovaleric Acidemia (IVA) is one of the Organic Acidemias. IVA is a hereditary metabolic disorder that prevents protein from properly breaking down in the system. The way it works is protein gets broken down into leucine (and other amino acids), which then breaks down into isovaleric acid. IVA is caused by an enzyme that isn't working right, so the isovaleric acid doesn't get broken down properly. This causes the isovaleric acid to build up in the body, which can affect the brain and nervous system if left untreated. The results can be retardation, loss of motor skills, seizures, coma and eventually death, making early diagnosis and proper treatment essential.

Because of IVA's rarity, many doctors haven't had any exposure to it. This lack of exposure can lead to a delay in diagnosis or even a misdiagnosis. There have been cases originally thought to be Reye Syndrome that were later found to be IVA. Some cases of near SIDS (Sudden Infant Death Syndrome) have also been related to another metabolic disorder called MCAD or Medium Chain Acyl-CoA Dehydrogenase Deficiency.

This information did little to alleviate our fears when we found out that my nephew, Justice, has IVA; instead it prompted many questions...

How did Justice get IVA?

Everyone has two sets of genes; they get one set from their mother and one set from their father. Genes are like written instructions. And sometimes within these instructions there is a typo or error, called a mutation. Justice received, from both his parents, a mutated copy of the gene that makes the IVA enzyme, which left him without a fully functioning set of genes. The result was IVA. For parents who both possess this mutated gene there is a 25% chance, with each pregnancy, that the baby will have IVA.

Will Justice be okay?

IVA is a lifelong treatable disorder. Outcome varies from one person to the next, but with early detection the prognosis improves. Because IVA isn't outgrown, Justice will be on a lifetime diet of low protein foods along with a specialized formula.

The formula will give Justice the protein and amino acids he needs, minus the leucine. Limiting Justice's leucine intake limits the production, and subsequent build-up, of isovaleric acid in his system. But Justice still needs help ridding his body of extra isovaleric acid. For this, a supplement of carnitine, glycine, or a combination of both, can be used. In Justice's case, he's doing well on carnitine alone.

Carnitine helps produce muscle power. Isovaleric acid bonds to both carnitine and glycine, like metal to a magnet. The isovaleric acid is then converted to a less harmful compound, which is flushed out with urine.

What if Justice wasn't diagnosed early in life?

Untreated IVA can cause severe health problems such as: lethargy, coma, seizures, vomiting, acidosis, ataxia, mental retardation, elevated isovaleric acid, moderate to severe hyperammonemia, hypocalcemia, pancytopenia - neutropenia, thrombocytopenia, and/or anemia, and death soon after birth. Approximately half of the people with IVA have died before they could be diagnosed clinically, which reaffirms the need for expanded newborn screening (NBS). Nearly half of those that survived [late diagnosis] suffered mental retardation and severe loss of motor skills. Seizures are also common among patients diagnosed late.

Treated IVA patients can lead nearly normal lives, aside from the strict diet, supplements, extra caution in avoiding illnesses and regular monitoring by medical professionals. With early detection of IVA the prognosis and quality of life greatly improves.

What if Justice catches a cold or the flu?

Because our bodies release stored proteins when we're sick, common illnesses can cause Justice's isovaleric acid levels to rise. So we have to take extra precautions in protecting him against normal childhood illnesses like colds, flu and infection.

But when Justice does get sick, we can cut or omit protein from his diet and supplement with higher carbohydrates (foods high in sugar) to help slow the release of stored proteins. In addition, Justice's carnitine dosage may need to be increased.

What are the symptoms of an acute attack?

The symptoms of IVA can vary. But the typical symptoms are lethargy (sleeping more and becoming hard to wake up), loss of appetite, vomiting and the distinct smell of dirty socks. The "dirty socks" smell is caused by the build-up of isovaleric acid. This "dirty socks" smell has also been discribed as a "rancid cheese" smell.

Is there any good news about this disorder?

Yes! I'm happy to say that in recent years a lot has been learned about metabolic disorders. There's ongoing research in gene therapy that holds great promise for the future treatment of IVA and other metabolic disorders.

There have also been great advances in testing for metabolic disorders. IVA is one of the few that can be tested for prenatally. It can also be detected in the first few days of life with expanded newborn screening (NBS). This expanded screening is done using a technique called Tandem Mass Spectrometry (MS/MS).

How is Justice doing today?

When Justice was 5-years-old his developmental level was tested. He tested at the 6-year-old level and they said he was ready to start reading! This is amazing since doctors felt he would fall behind in school. Justice is now 7-years-old and continuing to thrive.

Because of Justice's diet, the doctors also predicted he would be at the low end of the "normal growth range", but he's actually big for his age. Justice is pretty much like every other kid except for the specialized diet, formulas, medications and lifetime monitoring by health care providers. He's smart, has good motor skills, talks up a blue streak, and is always trying to rule the roost with that welcome affliction known as the "terrible toddler stage".