Journal of Inherited Metabolic Disease

, Volume 34, Issue 6, pp 1127–1136

An update on molecular genetics of Alkaptonuria (AKU)


DOI: 10.1007/s10545-011-9363-z

Cite this article as:
Zatkova, A. J Inherit Metab Dis (2011) 34: 1127. doi:10.1007/s10545-011-9363-z


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.

Supplementary material

10545_2011_9363_MOESM1_ESM.pdf (713 kb)
Supplementary Table 1List of all HGD mutations reported thus far with allele frequencies (526 AKU chromosomes from 267 families). Country of origin and references are indicated for all patients. Country of the first patient reported is listed as first, the first mutation report is indicated in bold. The short name and the original name are indicated for mutations for which the numbering has changed due to the HGVS nomenclature recommendations. DNA numbering is based on cDNA (NM_000187.3), with +1 corresponding to the A of the ATG. Gray shading indicates the 23 most frequent mutations that have been found in 361/496 (72.8%) of the AKU chromosomes carrying identified mutations. Variants IVS9-56G>A* and IVS9-17G>A* were published as mutations, but Vilboux et al. (2009) reported that they are most likely benign variants. Mutations G115fs** (c.413_434+35del57) and V157fs** (c.470-1_494del25) are caused by genomic deletions that are predicted to cause exon 6 and 8 skipping, respectively, thus leading to frameshift and preliminary stop of translation. A question mark in the column “Nucleotide change” indicates that the exact change is unknown or a published change is inconsistent with the gene sequence.(PDF 713 kb)

Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  1. 1.Institute of Molecular Physiology and GeneticsSlovak Academy of SciencesBratislavaSlovakia
  2. 2.Department of Molecular Biology, Faculty of Natural SciencesComenius UniversityBratislavaSlovakia