AKU

Alkaptonuria (AKU), also known as black urine disease or ochronosis, is a rare genetic disorder that causes a deficiency in the enzyme homogentisate 1,2-dioxygenase (HGD). This deficiency leads to the accumulation of homogentisic acid (HGA) in the body, which can cause various symptoms and complications. AKU is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the faulty gene, one from each parent, to be affected by the condition.

Symptoms and Diagnosis

The most characteristic symptom of AKU is the darkening of the urine when it is exposed to air, which is where the name "black urine disease" comes from. However, this symptom may not always be noticed or may be attributed to other causes. As individuals with AKU age, they may develop more noticeable symptoms related to the accumulation of HGA, including:

• Dark spots on the sclera (white of the eye) and ear cartilage
• Darkening of the skin, particularly in areas exposed to sweat and friction
• Joint pain and stiffness due to the buildup of pigment in connective tissues, leading to early-onset osteoarthritis
• Heart valve abnormalities
• Kidney stones and other kidney complications

Diagnosis of AKU typically involves a combination of clinical evaluation, family history, and laboratory tests to measure the levels of HGA in the urine. Genetic testing can also confirm the presence of mutations in the HGD gene.

Treatment and Management

There is no cure for AKU, but treatment focuses on managing symptoms and reducing the risk of complications. Current management strategies include:

• High doses of vitamin C to reduce the oxidation of HGA, although its effectiveness is limited
• Pain management strategies for joint pain and stiffness
• Physical therapy to maintain joint function
• Regular monitoring for heart and kidney complications

In recent years, a drug called nitisinone has shown promise in reducing the levels of HGA in the body, potentially slowing the progression of the disease. However, its long-term effectiveness and safety are still under study.

Epidemiology

AKU is considered a very rare condition, with an estimated incidence of 1 in 250,000 to 1 in 1,000,000 live births worldwide. It occurs in all ethnic groups but is more common in certain populations due to the founder effect, such as in Slovakia and the Dominican Republic.

History

Alkaptonuria was one of the first genetic disorders to be recognized as such. It was first described in the medical literature in 1902 by Sir Archibald Garrod, who also coined the term "inborn error of metabolism" to describe conditions like AKU.

See Also

• Genetic disorder
• Autosomal recessive inheritance
• Osteoarthritis
• Inborn error of metabolism