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HPD gene

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

HPD gene

The HPD gene provides instructions for an enzyme essential to breaking down the amino acid tyrosine, and mutations in this gene can lead to metabolic disorders like tyrosinemia type III and hawkinsinuria.

Normal Function

The HPD gene provides instructions for making an enzyme called 4-hydroxyphenylpyruvate dioxygenase. This enzyme is abundant in the liver, with smaller amounts found in the kidneys. It is the second in a series of five enzymes that work to break down the amino acid tyrosine, a protein building block found in many foods.

Specifically, 4-hydroxyphenylpyruvate dioxygenase converts a tyrosine byproduct called 4-hydroxyphenylpyruvate to homogentisic acid. This acid is further broken down into smaller molecules that are either excreted by the kidneys or used to produce energy or make other substances in the body.

Health Conditions Related to Genetic Changes

Tyrosinemia

At least six HPD gene mutations have been identified that cause tyrosinemia type III. This condition is characterized by neurological problems, including intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia).

These mutations result in an enzyme that has unusually low activity or is absent. Consequently, the body cannot properly break down tyrosine, causing 4-hydroxyphenylpyruvate to be converted into toxic compounds instead of homogentisic acid. The buildup of these toxic compounds can impair cell function and cause cell death, particularly in the nervous system.

Other disorders

At least two HPD gene mutations have been found to cause a rare condition called hawkinsinuria. In infants, this condition is characterized by a failure to gain weight and grow at the expected rate (failure to thrive) and abnormally high acid levels in the blood (acidosis).

In this condition, decreased enzyme activity leads to the formation of an unusual sulfur-containing amino acid called hawkinsin. It remains unclear exactly how the production of hawkinsin leads to the specific features of the disorder.

Frequently Asked Questions

For tyrosinemia type III, concerning signs include unexplained seizures, significant developmental delays, or episodes of poor balance and coordination (ataxia). For hawkinsinuria in infants, a failure to gain weight and grow as expected (failure to thrive) combined with signs of abnormally high acid levels in the blood (acidosis), such as lethargy, poor feeding, or rapid breathing, are urgent indicators.
Diagnosis often begins with newborn screening, which can detect elevated levels of tyrosine or related metabolites in the blood. If screening is abnormal, further diagnostic tests include specific blood and urine amino acid analysis to measure levels of tyrosine and its byproducts, and genetic testing to identify mutations in the HPD gene, confirming the specific disorder.
Dietary management is critical and typically involves a strict low-tyrosine and low-phenylalanine diet to prevent the buildup of toxic compounds. This often requires special medical formulas and careful monitoring of protein intake from natural foods. Regular follow-up with a metabolic specialist and a registered dietitian is essential to ensure adequate nutrition while controlling amino acid levels.
Yes, both tyrosinemia type III and hawkinsinuria caused by HPD gene mutations are inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the mutated HPD gene (one from each parent) to develop the condition. Parents who each carry one copy of the mutated gene are typically unaffected but have a 25% chance with each pregnancy of having a child with the disorder.
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.