Isovaleric Acidemia, Metabolic Disorder, Organic acid condition Screening -Infant

Isovaleric Acidemia, Metabolic Disorder, Organic acid condition Screening -Infant

Isovaleric Acidemia, Metabolic Disorder, Organic acid condition Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The genetic screening for Isovaleric Acidemia is recommended.

B

Isovaleric acidemia is a rare disorder in which the body is unable to process certain proteins properly. It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.

OVERVIEW

Lack of isovaleryl-CoA dehydrogenase, which is involved in the metabolism of the branched chain amino acid leucine, results in the inability to break down isovaleric acid and the accumulation of potentially toxic metabolites. Clinical manifestations of the illness include an acute neonatal form, a chronic intermittent form, and a very mild form of unknown clinical significance.

SCREENING

Finding

Elevated C5 (isovaleryl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA

PREVALENCE

Incidence in the United States is approximately 1:159,000

INHERITANCE

Isovaleric acidemia is inherited in an autosomal recessive manner. It affects both boys and girls equally.

MATERNAL & FAMILY HISTORY

In most cases, there is no previous family history of this condition. Children develop normally during pregnancy. Mothers with isovaleric acidemia have had normal children.

PRENATAL TESTING

DNA testing or enzyme analysis by amniocentesis or CVS

CLINICAL CHARACTERISTICS

With early diagnosis and ongoing treatment, most affected children will have normal development. Without treatment, children with the chronic, intermittent form may suffer neurologic damage, though most children are developmentally normal. Those children with the acute neonatal form will present in the first few days or weeks of life and about half will die during their first episode. In many cases, the neonatal presentation occurs before the return of newborn screening results. After the neonatal period, symptoms may be triggered by consuming too much protein, and illness. Children may be healthy between metabolic crisis episodes. 

Initial symptoms may include:

  • A "sweaty feet" odor
  • Vomiting
  • Lethargy progressing to coma
  • Lab findings:
  1. Ketoacidosis
  2. Elevated ammonia levels in the blood
  3. Neutropenia, thrombocytopenia, anemia

EARLY SIGNS

There are two main forms of isovaleric acidemia (IVA), which differ by the age of onset. In one form, signs appear 1 to 14 days after birth. In the other form, signs of IVA do not appear until later in infancy or childhood (called chronic/intermittent IVA). These two forms share similar signs, but the signs of chronic/intermittent IVA are less severe than IVA in babies.

Signs of IVA include:

  • Poor appetite
  • Sleeping longer or more often 
  • Tiredness
  • Vomiting
  • A “sweaty feet” smell
  • Seizures

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

CAUSES

When we eat food, enzymes help break it down. Some enzymes help break down proteins into their building blocks, amino acids. Other enzymes break down these amino acids. In isovaleric acidemia (IVA), the enzyme isovaleryl-CoA dehydrogenase is not working correctly. 

This enzyme’s job is to breaks down the amino acid leucine. Babies with IVA either do not make enough or make non-working isovaleryl-CoA dehydrogenase. If your baby has IVA, his or her body cannot break down leucine. This results in the harmful buildup of organic acids in the body.

IVA is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for IVA, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with IVA is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment

Your baby will need to be on a carefully planned diet in order to avoid the proteins and amino acids (building blocks of proteins) that may trigger many of the signs mentioned in the Early Signs section. Your baby’s doctor may recommend special formulas or foods made for children with isovaleric acidemia (IVA). These formulas will likely continue through adulthood.

It is also important for your baby to eat often. Long periods of time without food, illnesses, and infections can also trigger many of the signs of IVA.

Supplements and Medication

Not all amino acids are bad for your baby. Leucine is the amino acid that cannot be broken down, but glycine is a helpful amino acid. Your baby might need glycine supplements to get rid of harmful organic acids that result from this condition. Your baby’s doctor can write a prescription for these supplements.

Your baby’s doctor might also prescribe L-carnitine supplements. L-carnitine is a natural substance, but your baby’s body might not make enough of it. These supplements can help remove harmful waste products from the body.

EXPECTED OUTCOMES

With early and careful treatment, your child will most likely have a healthy life with typical growth and development.

Without treatment, babies with isovaleric acidemia (IVA) can suffer brain damage or even die within the first year of life.