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HADHA gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

HADHA gene

The HADHA gene provides instructions for creating a critical component of the mitochondrial trifunctional protein, which is essential for converting fats into energy.

Overview

The HADHA gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This complex functions within mitochondria, the energy-producing centers of cells. The protein is composed of eight subunits: four alpha subunits produced from the HADHA gene and four beta subunits produced from the HADHB gene.

The mitochondrial trifunctional protein contains three enzymes essential for fatty acid oxidation, a process that breaks down fats to convert them into energy. The alpha subunits contain two of these enzymes: long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 2-enoyl-CoA hydratase. This protein is specifically required to metabolize long-chain fatty acids, which are found in foods like milk and certain oils and serve as a major energy source for the heart, muscles, and liver.

Health Conditions Related to Genetic Changes

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Mutations in the HADHA gene can cause long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. These mutations decrease the activity of the specific enzyme responsible for long-chain 3-hydroxyacyl-CoA dehydrogenase. Common effects include:

  • Alteration of the alpha subunit structure, preventing normal function.
  • Inability to metabolize long-chain fatty acids, leading to a lack of energy (lethargy) and low blood glucose (hypoglycemia).
  • Accumulation of partially metabolized fatty acids, which can damage the liver, heart, muscles, and the retina.

Mitochondrial trifunctional protein deficiency

Certain HADHA mutations reduce all three enzyme activities of the mitochondrial trifunctional protein. This results in:

  • Decreased levels of the protein complex.
  • Disruption of the metabolic process, causing lethargy and hypoglycemia.
  • Tissue damage in the liver, heart, and muscles due to the buildup of unprocessed fatty acids.

Other disorders

In rare cases, HADHA mutations are linked to an increased risk of serious liver disorders during pregnancy, specifically acute fatty liver of pregnancy (AFLP) and HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelets). This risk is higher when a woman carries a mutation in one copy of the HADHA gene and the fetus carries two copies of a mutation.

Frequently Asked Questions

Patients should limit long‑chain fatty acids (e.g., dairy, certain oils) and increase medium‑chain triglycerides (MCTs) in the diet. Regular, balanced meals help maintain blood glucose, and a low‑fat, high‑carbohydrate diet is often advised. A registered dietitian experienced with metabolic disorders should tailor the plan.
Initial screening involves measuring plasma acyl‑carnitine profiles, looking for elevated C14:1 or C16:1 species. Confirmation requires DNA sequencing of the HADHA gene to identify pathogenic variants. A liver or muscle biopsy with enzymatic activity assays can also be used if needed.
Key red flags include unexplained hypoglycemia, lethargy, vomiting, or cardiomyopathy in infants or young children, especially after fasting or illness. Elevated liver enzymes, muscle pain, or vision changes may also suggest the disorder.
Many newborn screening programs include an acyl‑carnitine panel that can flag elevated long‑chain species suggestive of LCHAD. A positive screen triggers confirmatory genetic testing and early referral to a metabolic specialist. Early intervention can prevent severe complications such as cardiomyopathy or sudden death.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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