Reversal of clinical symptoms and radiographic abnormalities with protein restriction and ascorbic acid in alkaptonuria

There is no definitive treatment protocol for alkaptonuria. A patient with alkaptonuria was treated with ascorbic acid (0.5 g/day) from the age of 4 years. He developed episodes of severe recurrent joint pain at 9.5 years of age after which a protein-restricted diet (1.3 g/kg/day) was started. Protein restriction in combination with ascorbic acid therapy (1 g/day in two divided doses) resulted in a significant decrease but not a normalization of the urinary homogentisic acid excretion. Joint pain resolved and the radiological evidence of 'moth-eaten' irregularities on the articular surface in both knees disappeared. He is currently well, growing normally and in nitrogen balance. Our findings document a reversal of bone abnormalities and clinical symptoms in a case of alkaptonuria. The results should be confirmed in a larger study. We suggest that protein restriction should be applied in combination with ascorbic acid in affected patients as soon as joint pain occurs.