Epidemiology
Etiology
Mutation in the HGD gene
Pathophysiology
- Lack of functional homogentisic acid dioxygenase → impaired conversion of homogentisate to 4-maleylacetoacetate
- Accumulation of homogentisate → tissue discoloration and organ damage
Clinical features
- Usually, a benign condition
- Ochronosis: bluish-black discoloration of connective tissues
- Affects cartilage (e.g., ears), tendons, skin, and/or sclera
- Body fluids (e.g., urine, sweat) often turn black when exposed to air
- The urine in an affected baby’s diaper often darkens after several hours. Clothing may show brownish stains from perspiration. The late darkening is caused by the oxidation of homogentisic acid in body fluids.
- Calcifications of the following
- Cartilage: arthritis (ochronotic osteoarthropathy)
- May manifest with arthralgias due to accumulation of homogentisic acid, which attacks cartilage, in the joints
- Degenerative changes in the vertebral column
- Kidneys: nephrolithiasis
- Cartilage: arthritis (ochronotic osteoarthropathy)