Alkaptonuria, also called black urine disease, is a rare inherited metabolic disorder characterized by dark brown or black urine and arthritis in adulthood. Arthritis is a condition in which inflammation and swelling in the joints cause pain.
Alkaptonuria is caused by a defect, or mutation, in the HGD gene. This gene provides instructions for making an enzyme called homogentisic acid oxidase (HGAO). Normally, HGAO helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Patients with alkaptonuria do not have enough HGAO. As a result, a substance called homogentisic acid, which is produced when phenylalanine and tyrosine are improperly broken down, accumulates in the body.
Excess homogentisic acid accumulates in the blood and is deposited in connective tissues, such as those found in and around joints. By age 40, patients develop ochronosis, a blue-black discoloration of connective tissue, including bone, cartilage, and skin, caused by deposits of ochre-colored pigment. Over time, a buildup of this substance causes cartilage and heart valves to become brittle and weakened. Buildup of homogentisic acid in the joints leads to arthritis.
Homogentisic acid is also excreted in urine, making the urine turn dark when exposed to air. Dark staining of the diapers sometimes can indicate alkaptonuria in infants, but most patients are not aware they have the disease until they are 30 to 40 years of age. Males tend to have an earlier onset of arthritic symptoms with a greater degree of severity than females, although the reason for this difference is unclear. Alkaptonuria is not life-threatening. Patients typically require lifelong treatment to manage symptoms, but they are expected to live relatively normal, healthy lives. Treatment may include dietary modifications and anti-inflammatory medications.
Alkaptonuria is usually diagnosed based on symptoms of joint discomfort and skin discoloration. The diagnosis is confirmed by verifying family history of the disease, examining skin cells under a microscope, and testing the urine for homogentisic acid. A high urinary level of homogentisic acid is defined as greater than 4-8 grams in a 24-hour period. Homogentisic acid is not normally excreted in the urine of healthy individuals at all. Because many patients do not show dark urine, looking for high levels of homogentisic acid in the body fluids of all patients with osteoarthritis is recommended.
Because alkaptonuria is inherited, the only known risk factor is a family history of the disorder. Men and women are affected in equal numbers. The prevalence is estimated to be about one in 250,000 people worldwide. It is difficult to estimate the number of cases of alkaptonuria because newborn screening for alkaptonuria is not widely practiced and some people who have a mutation that causes the disorder do not show symptoms.

Related Terms

Alcaptonuria, AKU, alcaptonuric ochronosis, ankylosis, arthritis, black urine, dark diapers, dark urine, HGA, homogentisate, homogentisic acid, homogentisic acid oxidase, homogentisic acid oxidase deficiency, homogentisuria, IEM, inborn error of metabolism, metabolic disorder, ochronosis, osteoarthritis, rheumatoid arthritis, tyrosine, vitamin C.