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Alkaptonuria (black urine disease, alcaptonuria or ochronosis) is a rare inherited genetic disorder of tyrosine metabolism. This is an autosomal recessive trait that is caused by a defect in the enzyme homogentisic acid oxidase (EC 22.214.171.124). The enzyme normally breaks down a toxic tyrosine byproduct, homogentisic acid (also called alkapton), which is harmful to bones and cartilage and is excreted in urine.
A distinctive characteristic of alkaptonuria is that ear wax exposed to air turns red or black (depending on diet) after several hours because of the accumulation of homogentisic acid. Similarly, urine exposed to air can become dark; this is useful for diagnosising young children using diapers. It is also possible to develop a black discoloration of the nails. In adulthood, but usually not before age forty, persons suffering from alkaptonuria develop progressive arthritis (especially of the spine), due to the long-term buildup of homogentisate in bones and cartilage. The urine is malodorous.
Presumptive diagnosis can be made by adding sodium or potassium hydroxide to urine and observing the formation of a dark brown to black pigment on the surface layer of urine within 30 minutes to 1 hour. Diagnosis can be confirmed by demonstrating the presence of homogentisic acid in the urine. This may be done by paper chromatography and thin-layer chromatography.
Prevention is not possible and the treatment is aimed at ameliorating symptoms. Reducing intake of the amino acids phenylalanine and tyrosine to the minimum required to sustain health (phenylalanine is an essential amino acid) can help slow the progression of the disease.
Alkaptonuria was one of the four diseases described by Sir Archibald Edward Garrod, as being the result of the accumulation of intermediates due to metabolic deficiencies. He linked ochronosis with the accumulation of alkaptans in 1902, and his views on the subject were summarised in a 1908 Croonian lecture at the Royal College of Physicians. While Garrod identified it as a recessive condition, its genetic basis was not elucidated until 1996, when it was linked to HGO mutations.
- Garrod AE (1902). The incidence of alkaptonuria: a study in clinical individuality. Lancet 2: 1616−1620. Reproduced in Yale J Biol Med 75:221-31 (2002). PMID 12784973.
- Garrod AE (1908). The Croonian lectures on inborn errors of metabolism: lecture II: alkaptonuria. Lancet 2: 73–79.
- Fernández-Cañón JM, Granadino B, Beltrán-Valero de Bernabé D; et al. (1996). "The molecular basis of alkaptonuria". Nat. Genet. 14 (1): 19–24. doi:10.1038/ng0996-19. PMID 8782815.