LONG-TERM FOLLOW-UP OF 77 PATIENTS WITH ISOLATED METHYLMALONIC ACIDEMIA

Four forms of isolated methylmalonic acidaemia (MMA-aemia) are known: two resulting from defective MMA-CoA mutase-apoenzyme activity (mut(0), mut-) and two from defective coenzyme (adenosylcobalamin) synthesis (cblA, cblB). Since the first report on the natural history of MMA-aemia by Matsui et al in 1983, greater knowledge of the disease, leading to earlier diagnosis and better treatment, lias resulted in longer survival of an increasing number of patients, including those with severe forms of the disease. As a result, long-term complications that influence outcome are becoming apparent. In 1983, we discovered renal impairment in a 12-year-old patient with the cblA defect who was slightly vitamin B-12-responsive and had an otherwise excellent clinical course. Glomerular function (creatinine clearance 45 ml/min per 1.73 m(2)) as well as certain tubular functions were impaired and there was hyperuricaemia. Chronic interstitial nephritis without evidence of urate nephropathy was demonstrated histologically (Baumgartner et al 1989). In addition, arterial hypertension developed at 17 years of age. Subsequently several other reports of chronic renal failure have appeared (Waiter et al 1989; D'Angio et al 1991; Molteni et al 1991; Rutledge et al 1993). This experience prompted us to evaluate critically the clinical outcome in patients with MMA-aemia in relation to the type of defect, quality of treatment and degree of metabolic control. Our study includes 77 patients from 7 European countries whose fibroblasts were referred to us for enzyme analysis during the last 20 years. This preliminary report summarizes the results and highlights renal complications.