Ochronosis

Ochronosis is named for the reddish-brown hue of tissue termed "ochre-like" that was first described by a young physician named Archibald Garrod in the early-19th century. In what he called an "inborn error of metabolism," Archibald Garrod changed history when he coined that term for the obscure "black urine" disease, alkaptonuria. He proposed that ochronosis was due to deposition of a phenolic compound – "alkaptons" polymerizing into connective tissue - because the enzyme that could cleave it was absent and was inherited as a "chemical individuality." This was insightful work given that this preceded the conceptualization of genes. The work of Dr. Garrod would build core foundations on how we understand biochemistry, genetics, and medicine today. Alkaptonuria is iconic for being the initial description of the prototypical autosomal recessive disease. Today we know that expression of the homogentisate 1,2 dioxygenase becomes stunted because of mutations arising in the HGD gene, described as Dr. Garrod's "chemical individuality." Serum levels of homogentisic acid (Alkaptons) concomitantly rise and polymerize into tissue over time. The sequestration effect is also termed as endogenous ochronosis. This article reviews this and the exogenous form of ochronosis, commonly seen as a side-effect of medications that competitively inhibit the same enzyme mentioned above. In contrast to endogenous ochronosis, the deposition is often limited to the skin.