Genetics of alkaptonuria – an overview

Abstract

AbstractAlkaptonuria (AKU) is the first described inborn error of metabolism and a classical example of rare autosomal recessive disease. AKU patients carry homozygous or compound heterozygous mutations of the gene coding for enzyme homogentisate dioxygenase (HGD) involved in metabolism of tyrosine. The metabolic block in AKU causes accumulation of homogentisic acid (HGA) that, with advancing age of the patient, leads to severe and painful ochronotic arthropathy.HGDgene was mapped to chromosome 3q13.3 and is composed of 14 exons. In about 400 patients, 142 pathogenic variants were reported that are listed inHGDmutations database (http://hgddatabase.cvtisr.sk/). In this review, we summarise different aspects of AKU genetics and impact of theHGDvariants on enzyme function.