Makindo Medical Notes

🧬 Alkaptonuria is a rare autosomal recessive metabolic disorder. It leads to accumulation of homogentisic acid → dark pigmentation of connective tissues (ochronosis) + early arthritis. Classically: urine that darkens on standing! ⚗️

ℹ️ About

• Autosomal recessive inherited cause of arthritis.
• Dark pigmentation of cartilage and connective tissues = Ochronosis.

⚙️ Aetiology

• Deficiency of homogentisic acid oxidase.
• Enzyme encoded on chromosome 3q.
• Accumulated homogentisic acid binds collagen → tissue fragility and degeneration.

👩‍⚕️ Clinical Features

• 👁️ Blue-black pigmentation of sclerae and ear cartilage (first sign).
• 🦴 Crystal deposition in joints → destructive arthritis, especially spine, hips, knees.
• 🎧 Ochronosis: darkening of pinna and cartilage.
• 🧴 Sweat and connective tissues may be pigmented.
• ⚗️ Urine clear on voiding, but turns dark on standing or with alkali.
• Early-onset osteoarthritis due to brittle, pigmented cartilage.

🔬 Investigations

• Urine darkens on exposure to air or alkali (bedside clue!).
• Confirm with ↑ urinary homogentisic acid (GC-MS or HPLC).
• Genetic testing for HGD gene mutation if needed.

💊 Management

• Low protein diet (↓ phenylalanine & tyrosine intake).
• Vitamin C (ascorbic acid) → may ↑ renal clearance of homogentisic acid.
• Symptomatic management of arthritis (analgesia, physio, joint replacement if severe).
• Experimental: Nitisinone (tyrosine metabolism inhibitor) reduces homogentisic acid production.