Alkaptonuria and ochronosis in three siblings. Ascorbic acid treatment monitored by urinary HGA excretion

Patients with alkaptonuria lack homogentisate 1,2-dioxygenase leading to retention of homogentistic acid (HGA) in body fluids and eventually to tissue deposition of oxidation products, giving rise to the clinical picture of ochronosis. Ascorbic acid is a known inhibitor of the enzyme which catalyses the oxidation of homogentisic acid (HGA) to the polymer with affinity for collagen and was used in the treatment of three siblings with alkaptonuria. Ascorbic acid 500 mg bid was administered for 12 months. Two of the siblings tolerated the treatment, and in one the symptoms improved, whereas in the other they worsened. Plasma and urinary levels of HGA were monitored with a new HPLC method. Ascorbic acid is not effective in the treatment of symptomatic ochronosis.