Acidemia (Isovaleric)

Definition

Definition of Acidemia (Isovaleric)
Isovaleric acidemia, also called isovaleric aciduria or isovaleric acid CoA dehydrogenase deficiency, is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.

Symptoms

Symptoms of Acidemia (Isovaleric)
A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.

Genetics

Genetics of Acidemia (Isovaleric)
The disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Causes

Causes of Acidemia (Isovaleric)
There are various causes of Acidemia (Isovaleric):

1. Blood conditions
2. Genetic conditions
3. Metabolic conditions
4. Congenital conditions - metabolic disorders
5. Congenital conditions
6. Acid-base imbalance

Diagnosis

Diagnosis of Acidemia (Isovaleric)
The urine of newborns can be screened for isovaleric acidemia using mass spectrometry, allowing for early diagnosis. Elevations of isovalerylglycine in urine and of isovalerylcarnitine in plasma are found.

Treatment

Treatment of Acidemia (Isovaleric)
Treatment consists of dietary protein restriction, particularly leucine. During acute episodes, glycine is sometimes given, which conjugates with isovalerate forming isovalerylglycine, or carnitine which has a similar effect.

Elevated hydroxyisovalerate is a clinical marker of biotin deficiency. Without biotin, leucine and isoleucine cannot be fully metabolized. This leads to the formation of hydroxyisovalerate instead of the normal useful byproducts of leucine and isoleucine catabolism. Elevated hydroxyisovalerate can be caused by genetic conditions or dietary deficiency of biotin, and many patients with organic acidemias related to incomplete leucine catabolism can benefit from supplemental biotin. Biotin deficiency on its own can have severe physiological and cognitive consequences that closely resemble symptoms of organic acidemias.

Prognosis

Prognosis of Acidemia (Isovaleric)
Prognosis of IVA is highly variable, depending on residual isovaleryl co-A dehydrogenase activity, diet in infancy and childhood, age at diagnosis, treatment both at home and during crises, adherence to treatment, and other factors. In those diagnosed late, nursing v. bottle feeding may be a factor as cow and soy based formulas have higher protein content than breastmilk.

While some patients die in infancy, others have lived into adulthood with little or no neurological impairment. At least one patient is a certified physics and math teacher with two children despite negligible isovaleryl co-a dehydrogenase activity.