Rare osteoarthritis: ochronosis and Kashin-Beck disease

normally retained in the body because of its high renal clearance; the absence of the HGD enzyme leads to abundant urinary excretion of homogentisic acid, which darkens slowly upon oxidation by prolonged exposure to air. The darkening is hastened by the addition of alkali to the urine and is reflected in the original term for homogentisic acid, alkapton, which refers to its avidity for alkali. The distinctiveness of alkaptonuria accounts for reports of dark urine, including urine “as black as ink,” dating as far back as the Middle Ages. There has even been biochemical confirmation that ochronotic pigment in the bone and articular hip cartilage of an Egyptian mummy originated from homogentisic acid, which demonstrates that this disorder has afflicted humans since ancient times.