HGD and alkaptonuria: AKU is a rare genetic inborn disease that affects protein metabolism; it is caused by a deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid to maleylacetoacetic acid in the tyrosine degradation pathway.[6] AKU arises from homozygous or compound heterozygous mutations in the homogentisate 1,2-dioxygenase gene, and there have been 212 unique AKU mutations.[12] AKU mutations are distributed throughout the homogentisate 1,2-dioxygenase gene with some prevalence in exons 3, 6, 7, 8, and 13.[13]