Isovaleric acidemia

Isovaleric acidemia (IVA), also known as isovaleric acid CoA dehydrogenase deficiency or "sweaty feet syndrome," is a rare inherited disorder of leucine metabolism caused by a deficiency of the enzyme isovaleryl-CoA dehydrogenase. This enzyme is essential for the normal breakdown of the branched-chain amino acid leucine. When the enzyme is deficient, isovaleric acid and related metabolites accumulate in the blood and tissues, leading to metabolic acidosis and potential toxicity to the central nervous system and other organ systems. Isovaleric acidemia presents in two main clinical forms. The acute neonatal form manifests within the first few days of life with poor feeding, vomiting, lethargy, seizures, and a characteristic odor of sweaty feet caused by the accumulation of isovaleric acid. Without prompt treatment, this form can progress rapidly to metabolic crisis, coma, and death. The chronic intermittent form is milder, with episodes of metabolic decompensation triggered by infections, increased protein intake, or physiological stress, often presenting later in infancy or childhood. Some individuals identified through newborn screening may remain asymptomatic with appropriate management. Treatment of isovaleric acidemia focuses on dietary management with leucine restriction, supplementation with glycine and L-carnitine (which help conjugate and eliminate excess isovaleric acid), and aggressive management of acute metabolic crises with intravenous glucose, hydration, and temporary protein restriction. Long-term outcomes have improved significantly with early detection through expanded newborn screening programs and proactive metabolic management. Despite treatment, some patients may experience developmental delays or intellectual disability, particularly if they have experienced severe neonatal crises.

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