Sequence analysis of the homogentisate 1,2 dioxygenase gene in a family affected by alkaptonuria

Editor—Alkaptonuria (AKU) is a disorder of the catabolism of aromatic amino acids. A defect of homogentisate 1,2 dioxygenase (HGO) leads to an accumulation of homogentisic acid (HGA) and subsequently to deposition of polymerised HGA, a brown-black pigment, in connective tissue, primarily in cartilage.1 2This phenomenon is known as ochronosis. It results in debilitating arthropathy which typically becomes manifest in the fourth decade of life. Large amounts of HGA are excreted in the urine and cause its black discolouration upon oxidation. In 1891, homogentisic acid was first isolated by Wolkow and Baumann3 from the urine of an AKU patient from a remote area of the Black Forest in south western Germany. In 1902, Garrod, aware of this biochemical finding, observed the autosomal recessive mode of inheritance of AKU and thereby showed for the first time that mendelian laws also apply to human genetics.4 Garrod postulated that AKU results from an enzyme deficiency and introduced the concept of the “inborn error of metabolism”.5 Recently, the human gene encoding HGO was cloned by Fernadez-Canon et al .6Two different …