Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Alkaptonuria

Reviewed November 2013

What is alkaptonuria?

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.

How common is alkaptonuria?

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.

What genes are related to alkaptonuria?

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.

Related Gene(s)

Changes in this gene are associated with alkaptonuria.

  • HGD

How do people inherit alkaptonuria?

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.

Where can I find information about diagnosis or management of alkaptonuria?

These resources address the diagnosis or management of alkaptonuria and may include treatment providers.

  • DevelopAKUre (http://www.developakure.eu/)
  • Gene Review: Alkaptonuria (http://www.ncbi.nlm.nih.gov/books/NBK1454)
  • Genetic Testing Registry: Alkaptonuria (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0002066)
  • MedlinePlus Encyclopedia: Alkaptonuria (http://www.nlm.nih.gov/medlineplus/ency/article/001200.htm)

You might also find information on the diagnosis or management of alkaptonuria in Educational resources (http://www.ghr.nlm.nih.gov/condition/alkaptonuria/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/alkaptonuria/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about alkaptonuria?

You may find the following resources about alkaptonuria helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for alkaptonuria?

  • AKU
  • alcaptonuria
  • homogentisic acid oxidase deficiency
  • homogentisic acidura

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about alkaptonuria?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding alkaptonuria?

acids ; alkaptonuric ochronosis ; arthritis ; autosomal ; autosomal recessive ; cartilage ; cell ; deficiency ; enzyme ; gene ; incidence ; inherited ; kidney ; kidney stones ; metabolism ; ochronosis ; oxidase ; phenylalanine ; pigment ; pigmentation ; prostate ; recessive ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Alkaptonuria (http://www.ncbi.nlm.nih.gov/books/NBK1454)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10768658?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/14978662?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12501223?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/23486607?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/21720873?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2013
Published: December 16, 2014