Alkaptonuria

Alkaptonuria is a rare inherited metabolic disorder caused by mutations in the HGD gene, which normally produces the enzyme homogentisate 1,2-dioxygenase. Without a functioning enzyme, the body cannot fully break down the amino acids tyrosine and phenylalanine, and the intermediate compound homogentisic acid builds up in blood and tissue. The condition follows an autosomal recessive inheritance pattern, so a child is affected only when both parents pass on a mutated copy of the gene. Its earliest visible sign is urine that darkens on standing or exposure to air, present from birth, which historically earned it the nickname black urine disease. Over decades the accumulated acid deposits as a dark pigment in cartilage and connective tissue, a process called ochronosis, leading in adulthood to joint pain and arthritis in weight-bearing joints, along with a real risk of heart valve disease and kidney stones. Alkaptonuria affects roughly one in 250,000 people worldwide, though it is markedly more common in Slovakia and the Dominican Republic.