Inheritance: usually autosomal recessive
Enzyme defect: HGO gene (homogentisate 1,2-dioxygenase)
Clinical findings - genitourinary:
(1) urine that darkens on standing or with exposure to alkali (as homogentisic acid oxidizes to a melanin-like product)
(2) recurrent renal stones
(3) prostate stones in men, often with prostatitis
Clinical findings - soft tissue:
(1) ochronosis, with dark discoloration of cartilage, tendons, sclera and ear cartilage (may not become apparent until after age 40)
(2) thickening of the Achilles tendon
(3) muscle, ligament or tendon tears after minimal trauma
Clinical findings - cardiovascular:
(1) dilatation of the aorta, with potential for aneurysm formation
(2) aortic valve calcification and/or regurgitation
(3) mitral valve calcification and/or regurgitation
(4) coronary artery disease with calcifications
Clinical findings - articular:
(1) low back pain, often at a young age (about half of patients before age 30, almost all by age 40), with extensive calcification of the intervertebral discs
(2) kyphosis with decreased lumbar flexion
(3) height loss
(4) chronic joint pain, usually starting at an early age
Clinical findings - other:
(1) discoloration of clothing exposed to sweat
(2) affected siblings
Confirmation of the diagnosis is by demonstrating a high serum or urinary concentration of homogentisic acid. Normally serum levels are undetectable, while urine levels are < 0.01 mmol per mmol creatinine.
