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.

Normally, the body breaks down proteins from food into smaller parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with isovaleric acidemia have inadequate levels of an enzyme that helps break down a particular amino acid called leucine.

Isovaleric acidemia (IVA) is caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase, leading to accumulation of isovaleryl-CoA and its metabolites including free isovaleric acid, 3-hydroxyisovalerate and N-isovalerylglycine.

Isovaleric acidemia is estimated to affect at least 1 in 250,000 people in the United States.

Why Nutrition Management is important?

The major goal of IVA management is to reduce the production and increase excretion of isovaleryl-CoA. This is achieved by: 1) limiting leucine intake via protein restriction; 2) enhancement of alternative metabolic pathways using carnitine and glycine, which conjugate with isovaleryl-CoA to produce the non-toxic compounds isovalerylglycine and isovalerylcarnitine; and 3) application of an emergency management protocol at times of metabolic stress (e.g. illness and fasting).

The aim is to limit the dietary leucine intake and minimize formation of isovaleric acid, which can be managed through diet. Sufficient leucine must be given for normal growth requirements, hence complete protein restriction is equally harmful for the child. Usually a modest protein restriction 2g/kg in infant, then decrease to 1.0 -1.5g/kg in young children, and combined with adequate energy intake is sufficient to limit the production of isovaleric acid. It is also important to supplement the child with vitamins and minerals.