ALKAPTONURIA
Alkaptonuria is a rare genetic disorder that is characterized by the accumulation of homogentisic acid (HGA) in the body.
- Affected individual’s body can’t produce enough of an enzyme called homogentisic dioxygenase (HGD) used to break down homogentisic acid.
- This results in the buildup of homogentisic acid in the body.
- The condition is estimated to occur in 1 in every 250,000 people, but it is more common in Slovakia and the Dominican Republic.
- Although this condition does not reduce life expectancy, it significantly affects the quality of life.
CAUSES
Alkaptonuria is a genetic disorder inherited in an autosomal recessive genetic pattern.
An autosomal recessive genetic pattern is one of the several ways that a trait disorder can be passed down through families
Autosomal recessive occurs when two abnormal genes are inherited, one from each parent. This means that both parents must carry the defective gene and transmit the gene to the child for the child to have the condition.
A mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase causes the condition.
This defect makes the body unable to process or break down the amino acids phenylalanine and tyrosine.
As a result, the body accumulates an intermediate substance called homegentisic acid in the blood and other body tissues.
SYMPTOMS
- Dark discoloration of the urine. This is usually present from birth and may appear on the baby’s diaper as dark stains. The urine of affected individual turns black upon long-standing exposure to air.
Additional symptoms usually develop in middle adulthood (around age 30) when joint and other problems occur. These symptoms are due to chronic accumulation of homogentisic acid in connective tissues, they may include:
- Discoloration of the sclera (white) in the eyes. This pigmentation does not interfere with vision.
- Chronic joint pain and inflammation (arthritis) especially in the spine and large joints. This can be severe and disabling.
- Kidney stones, which develop in 50% of affected individuals over 64 years of age.
- Prostrate stones in men
- Dark-colored sweat or sweat stains
- Thickened, irregular and discolored grey or black cartilage in the ears
- Blue speckled discoloration of the skin
- Heart disease which may result from the accumulation of the homogentisic acid within the mitral or aortic valves.
- Hardening of the blood vessel which may raise the risk of high blood pressure.
DIAGNOSIS AND TREATMENT
Diagnosis is made upon identification of characteristic symptoms, detailed patient history, and thorough clinical evaluation.
Alkaptonuria is usually suspected in individuals with dark urine after exposure to air.
A test called gas chromatography-mass spectrometry analysis may be used to look for traces of homogentisic acid in your urine. Identification of elevated levels of the acid may be suggestive of the condition.
Genetic testing to detect mutations in the HGD gene can also be used.
An echocardiogram may be recommended for individuals over 40 to detect cardiac complications.
Imaging tests such as CT scan can also be recommended
TREATMENT
No specific treatment exists for the condition. Treatment options are however aimed at the specific symptoms present in each individual as well as preventing and relieving possible complications such as arthritis, heart disease, and kidney stones
They may include:
- Severe restriction of protein intake. You may be put on a low-protein diet.
- Large doses of vitamin C may be recommended. This hinders the accumulation and deposition of homogentisic acid.
- Anti-inflammatory medications for joint pain
- Physical and occupational therapy to help maintain flexibility and strength in the muscles and joints.
- At some point, surgery may also be needed. It has been reported that about half of people with the condition will need a knee, hip, or shoulder replacement, often by age 50 or 60.
- Surgery may also be needed to replace the aortic or mitral heart valves if they stop working well.