Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.
This condition is rare, affecting 1 in 250,000 to 1 million people worldwide. Alkaptonuria is more common in certain areas of Slovakia (where it has an incidence of about 1 in 19,000 people) and in the Dominican Republic.
Mutations in the HGD gene cause alkaptonuria. The HGD gene provides instructions for making an enzyme called homogentisate oxidase. This enzyme helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Mutations in the HGD gene impair the enzyme's role in this process. As a result, a substance called homogentisic acid, which is produced as phenylalanine and tyrosine are broken down, accumulates in the body. Excess homogentisic acid and related compounds are deposited in connective tissues, which causes cartilage and skin to darken. Over time, a buildup of this substance in the joints leads to arthritis. Homogentisic acid is also excreted in urine, making the urine turn dark when exposed to air.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Homogentisic acid oxidase deficiency
- Homogentisic acidura
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Introne WJ, Perry M, Chen M. Alkaptonuria. 2003 May 9 [updated 2021 Jun 10]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK1454/ Citation on PubMed
- Lubics A, Schneider I, Sebök B, Havass Z. Extensive bluish gray skin pigmentation and severe arthropathy. Endogenous ochronosis (alkaptonuria). Arch Dermatol. 2000 Apr;136(4):548-9, 551-2. Review. Citation on PubMed
- Mannoni A, Selvi E, Lorenzini S, Giorgi M, Airó P, Cammelli D, Andreotti L, Marcolongo R, Porfirio B. Alkaptonuria, ochronosis, and ochronotic arthropathy. Semin Arthritis Rheum. 2004 Feb;33(4):239-48. Citation on PubMed
- Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA. Natural history of alkaptonuria. N Engl J Med. 2002 Dec 26;347(26):2111-21. Citation on PubMed
- Ranganath LR, Jarvis JC, Gallagher JA. Recent advances in management of alkaptonuria (invited review; best practice article). J Clin Pathol. 2013 May;66(5):367-73. doi: 10.1136/jclinpath-2012-200877. Epub 2013 Mar 13. Review. Citation on PubMed
- Zatkova A. An update on molecular genetics of Alkaptonuria (AKU). J Inherit Metab Dis. 2011 Dec;34(6):1127-36. doi: 10.1007/s10545-011-9363-z. Epub 2011 Jul 1. Citation on PubMed