Short answer · Medically reviewed summary · Last updated: 2026-04-07

Isovaleric acidemia is a rare, inherited metabolic disorder where the body cannot properly break down the amino acid leucine, leading to the accumulation of toxic substances like isovaleric acid. If left unmanaged, this buildup can cause serious health complications, ranging from acute metabolic crises to developmental delays, though early diagnosis through newborn screening significantly improves long-term outcomes. What causes Isovaleric acidemia? Isovaleric acidemia is caused by mutations in the IVD gene, which provides instructions for making an enzyme called isovaleryl-CoA dehydrogenase.

What is Isovaleric acidemia

Name: What is Isovaleric acidemia
Creator: DiseaseMaps Editorial Team
Published: 2015-10-27UTC01:09:00.0000000

What is Isovaleric acidemia? Plain-language, medically reviewed definition plus the lived reality told by patients.

Isovaleric acidemia is a rare, inherited metabolic disorder where the body cannot properly break down the amino acid leucine, leading to the accumulation of toxic substances like isovaleric acid. If left unmanaged, this buildup can cause serious health complications, ranging from acute metabolic crises to developmental delays, though early diagnosis through newborn screening significantly improves long-term outcomes.

What causes Isovaleric acidemia?

Isovaleric acidemia is caused by mutations in the IVD gene, which provides instructions for making an enzyme called isovaleryl-CoA dehydrogenase. This enzyme is essential for breaking down leucine, a building block of proteins found in many foods. When this enzyme is deficient, toxic metabolic byproducts, specifically isovaleric acid, build up in the blood and tissues. This buildup acts like a metabolic toxin, disrupting normal cellular function and causing the characteristic "sweaty feet" odor often associated with the condition due to the accumulation of isovaleric acid.

How does Isovaleric acidemia affect the body?

The clinical presentation of isovaleric acidemia can vary widely between individuals. The condition primarily affects the metabolic system, but the neurological and hematological systems are also frequently involved. Common clinical manifestations include:

Metabolic Crises: Often triggered by illness, stress, or high protein intake, these episodes involve severe vomiting, lethargy, and metabolic acidosis.

Neurological Impact: If not treated promptly, high levels of toxins can lead to seizures, developmental delays, or intellectual disability.

Bone Marrow Suppression: Many patients experience pancytopenia, a reduction in red blood cells, white blood cells, and platelets.

Distinctive Odor: A hallmark sign is a strong, sweaty feet-like odor during episodes of illness.

How common is this condition?

Isovaleric acidemia is estimated to occur in approximately 1 in 250,000 to 1 in 500,000 individuals worldwide, though incidence rates can vary by geographic region and population. Because it is an autosomal recessive disorder, both parents must carry a copy of the mutated gene for a child to be affected. There is no gender predilection; both males and females are affected equally. At DiseaseMaps.org, 23 people with isovaleric acidemia have already joined our community to share their experiences and support one another.

What are the primary clinical forms?

Physicians generally categorize isovaleric acidemia into two main clinical forms based on the age of onset and severity:

Acute Neonatal Form: Presents within the first few days of life with severe metabolic acidosis, vomiting, and potential coma. This is a medical emergency.

Chronic Intermittent Form: Symptoms may not appear until later in infancy or childhood, often triggered by infections or dietary changes, leading to episodic illness and potential long-term growth or developmental issues.

How is it differentiated from other conditions?

It is important to distinguish isovaleric acidemia from other organic acidemias. While many metabolic disorders present with metabolic acidosis, the presence of elevated isovalerylglycine in urine and the specific "sweaty feet" odor are key diagnostic markers. Confirmatory testing usually involves molecular genetic testing of the IVD gene and biochemical assays to measure enzyme activity.

Next steps

Consult a metabolic specialist or a clinical geneticist to discuss testing and personalized management plans.

Ensure that your child is screened via state-mandated newborn screening programs if you suspect symptoms.

Connect with the 23 community members at DiseaseMaps.org who are living with or caring for someone with this condition.

Work with a specialized metabolic dietitian to establish a protein-restricted diet tailored to your specific clinical needs.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.