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HSD17B4 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

HSD17B4 gene

The HSD17B4 gene provides instructions for creating the D-bifunctional protein, an enzyme essential for breaking down fatty acids within the body's cells.

Normal Function

The HSD17B4 gene provides instructions for making the D-bifunctional protein. This protein is an enzyme that facilitates two specific biochemical reactions. It is located in peroxisomes, which are sac-like cell structures containing various enzymes used to break down substances.

The D-bifunctional protein is involved in the breakdown of fatty acids. It contains two separate regions, or domains, known as the hydratase and dehydrogenase domains. These domains carry out the second and third steps of the peroxisomal fatty acid beta-oxidation pathway. This process shortens fatty acid molecules until they are converted into acetyl-CoA, which is then transported out of the peroxisomes for cellular reuse.

Health Conditions Related to Genetic Changes

D-bifunctional protein deficiency

More than 60 HSD17B4 gene mutations have been identified in individuals with D-bifunctional protein deficiency, a severe disorder characterized by neurodegeneration beginning in infancy. Mutations can affect one or both enzymatic activities of the protein, though this does not appear to alter the severity of the disorder.

  • Impairment of these enzymatic activities prevents the efficient breakdown of fatty acids, causing them to accumulate in the body.
  • This accumulation may lead to abnormal brain development and the breakdown of myelin, the protective covering of nerves.
  • The destruction of myelin leads to a loss of white matter in the brain and spinal cord, a condition known as leukodystrophy.

Perrault syndrome

At least two HSD17B4 gene mutations have been linked to Perrault syndrome. This condition is characterized by hearing loss in both males and females, and ovarian abnormalities in affected females. These mutations reduce the amount of functional D-bifunctional protein produced, though the specific impact on fatty acid breakdown remains unknown.

Other Names for This Gene

  • 17-beta-HSD 4
  • 17-beta-HSD IV
  • 17-beta-hydroxysteroid dehydrogenase 4
  • 17beta-estradiol dehydrogenase type IV
  • 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase
  • beta-hydroxyacyl dehydrogenase
  • beta-keto-reductase
  • D-3-hydroxyacyl-CoA dehydratase
  • D-bifunctional protein, peroxisomal
  • DBP
  • hydroxysteroid (17-beta) dehydrogenase 4
  • MFE-2
  • MPF-2
  • multifunctional protein 2
  • peroxisomal multifunctional enzyme type 2
  • peroxisomal multifunctional protein 2
  • PRLTS1
  • SDR8C1
  • short chain dehydrogenase/reductase family 8C, member 1

Frequently Asked Questions

Early symptoms often appear within the first few months of life and include poor feeding, vomiting, lethargy, seizures, and developmental delay. Neurologic examination may reveal hypotonia (low muscle tone) and abnormal reflexes. Because the disorder affects brain white matter, MRI typically shows leukodystrophy. Prompt recognition and referral to a metabolic or neurology specialist can lead to earlier diagnosis and management.
Yes. Certain HSD17B4 mutations are associated with Perrault syndrome, which includes sensorineural hearing loss in both sexes and ovarian dysgenesis in females. Carriers may develop progressive hearing loss, so audiologic evaluation is recommended. Early hearing intervention (hearing aids or cochlear implants) can improve communication and developmental outcomes.
Diagnosis involves a combination of biochemical tests and genetic analysis. Blood and urine samples are tested for elevated very‑long‑chain fatty acids (VLCFAs) and abnormal bile acid intermediates. A confirmatory genetic test (whole‑exome or targeted HSD17B4 sequencing) identifies pathogenic mutations. Early diagnosis is crucial for initiating supportive care and monitoring for complications.
There is no cure, but management focuses on supportive therapies: anticonvulsants for seizures, physical and occupational therapy for motor development, and dietary modifications to reduce VLCFA intake. Some patients benefit from a low‑fat, high‑protein diet and supplementation with medium‑chain triglycerides. Regular neurologic and metabolic follow‑up is essential to adjust treatment as the disease progresses.
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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