What is ochronosis (alkaptonuria)?
Ochronosis (also known as alkaptonuria) is a rare autosomal recessive defect in tyrosine catabolism caused by mutations of the HGD gene on chromosome 3 that result in a deficiency of homogentisate 1,2-dioxygenase (HGD). Notably, heterozygotes are unaffected even when challenged with high doses of the precursor amino acids. HGD catabolizes homogentisic acid (HA) to molecules that can be used in the tricarboxylic acid (Krebs) cycle. When HGD is absent, HA builds up, polymerizes, and is deposited in the tissue (skin, sclera, arterial walls, prostate, and ear) as a gray-brown to blue-black pigment. Microscopic visualization by Virchow demonstrated a yellowish or “ochre” tint to tissues, thus the name ochronosis . The urine of a patient with ochronosis darkens on addition of alkali. The original term for HA was alkapton, which referred to its avidity for alkali, hence the name alkaptonuria.
In rare cases, exogenous ochronosis causes blue-black cartilage pigmentation in individuals exposed to phenol, benzene, hydroquinone, or other noxious substances. Chronic minocycline use can also stain cartilage black.
