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HGD gene

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

HGD gene

The HGD gene provides instructions for making an enzyme that breaks down specific amino acids, and mutations in this gene cause the metabolic disorder alkaptonuria.

Normal Function

The HGD gene provides instructions for making an enzyme called homogentisate 1,2-dioxygenase, which is active mainly in the liver and kidneys. This enzyme participates in a multi-step process that breaks down two protein building blocks (amino acids), phenylalanine and tyrosine. These amino acids also play a role in making certain brain chemicals (neurotransmitters), hormones, and pigments.

Homogentisate 1,2-dioxygenase is responsible for a specific step in the breakdown of phenylalanine and tyrosine. It adds two oxygen atoms to homogentisic acid, converting it to another molecule called maleylacetoacetate. Other enzymes then break down maleylacetoacetate into smaller molecules that are used for energy or to make other products.

Health Conditions Related to Genetic Changes

Alkaptonuria

Hundreds of variants in the HGD gene have been found to cause alkaptonuria. This condition is characterized by:

  • Arthritis
  • Kidney stones
  • Areas of dark pigmentation
  • Dark urine

Most of the HGD gene variants change single amino acids in the homogentisate 1,2-dioxygenase enzyme, severely reducing its function. Without a fully functional enzyme, phenylalanine and tyrosine are not broken down properly, and homogentisic acid builds up in the body.

Excess homogentisic acid settles in connective tissues and forms a substance called ochronotic pigment, which causes cartilage and skin to darken. Over time, this pigment can build up and harden (calcify), leading to health problems. Excess homogentisic acid is also excreted in urine, which makes urine turn dark when it is exposed to air.

Frequently Asked Questions

The most noticeable early sign is dark urine, which turns black or dark brown when exposed to air (e.g., in a diaper or toilet). In infants, this might be seen as dark staining in diapers. Later signs, often not appearing until adulthood, include dark pigmentation in ear cartilage or the whites of the eyes, and joint pain.
Management often involves a low-protein diet, specifically limiting phenylalanine and tyrosine, to reduce the buildup of homogentisic acid. Vitamin C supplementation may also be recommended as an antioxidant. Regular exercise and avoiding activities that put excessive stress on joints can help manage arthritis symptoms.
Long-term complications include severe arthritis, particularly in the spine and large joints, which can lead to joint damage and immobility. Kidney stones and heart valve problems can also occur. Monitoring typically involves regular orthopedic evaluations, imaging studies (like X-rays or MRI) to check joint health, and kidney function tests.
lkaptonuria is an autosomal recessive genetic disorder. This means a person must inherit two copies of the mutated HGD gene (one from each parent) to develop the condition. If both parents are carriers (each having one mutated copy), there is a 25% chance with each pregnancy that their child will have alkaptonuria.
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.