Ochronosis
Ochronosis is a connective tissue disorder caused by homogentisic acid accumulation, leading to dark pigmentation and early degenerative joint disease.
Definition:
Ochronosis is the bluish-black discolouration of connective tissues due to the accumulation of homogentisic acid, commonly seen in alkaptonuria, a rare autosomal recessive metabolic disorder.
Pathophysiology:
Deficiency of homogentisate 1,2-dioxygenase enzyme
Leads to accumulation of homogentisic acid (HGA) in tissues
HGA binds to collagen in cartilage and tendons, causing pigmentation and brittleness
Clinical Features:
Dark pigmentation of ear cartilage, sclerae (Osler’s sign), and skin folds
Urine turns dark on standing (pathognomonic)
Progressive degenerative arthropathy, especially of the spine, hips, and knees
Tendon ruptures, calcifications
May also involve cardiac valves and kidneys
Orthopaedic Implications:
Early-onset osteoarthritis unresponsive to conventional treatments
Spine involvement is common: calcified discs, kyphosis, stiffness
Total joint arthroplasty often required at a younger age
Intraoperative tissues appear dark brown or black
Diagnosis:
Clinical suspicion + urine darkening
Urinary HGA elevated
Genetic testing for HGD mutations
Imaging: disc calcifications, joint space narrowing, osteophytes
Treatment:
No cure
High-dose vitamin C may reduce HGA accumulation (limited evidence)
Nitisinone reduces HGA levels (off-label in ochronosis)
Surgical treatment for degenerative changes (arthroplasty, spinal surgery)