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.


Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria, ochronosis, and ochronotic arthritis. The defect is caused by mutations in the HGD gene, which maps to the human chromosome 3q21-q23. AKU shows a very low prevalence (1:100,000-250,000) in most ethnic groups, but there are countries such as Slovakia and the Dominican Republic in which the incidence of this disorder rises to as much as 1:19,000. In this work, we summarize the genetic aspects of AKU in general and the distribution of all known disease-causing mutations reported so far. We focus on special features of AKU in Slovakia, which is one of the countries with an increased incidence of this rare metabolic disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Alkaptonuria / diagnosis
  • Alkaptonuria / enzymology
  • Alkaptonuria / epidemiology*
  • Alkaptonuria / genetics*
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 3 / genetics
  • DNA Mutational Analysis / methods*
  • Dominican Republic / epidemiology
  • Genetics, Population
  • Genotype
  • Global Health
  • Homogentisate 1,2-Dioxygenase / deficiency
  • Homogentisate 1,2-Dioxygenase / genetics*
  • Homogentisate 1,2-Dioxygenase / urine
  • Homogentisic Acid / urine
  • Humans
  • Incidence
  • Joint Diseases / genetics
  • Mutation / genetics*
  • Ochronosis / genetics
  • Phenotype
  • Slovakia / epidemiology
  • Topography, Medical


  • Homogentisate 1,2-Dioxygenase
  • Homogentisic Acid