3-methylglutaconic aciduria and hypermethioninaemia in a child with clinical and neuroradiological findings of Leigh disease

We report on a child with a clinical and neuroradiological picture consiste nt with Leigh disease and an unusual association of isolated hypermethionin aemia and 3-methylglutaconic aciduria. A low-methionine diet normalized bot h plasma methionine and urine 3-methylglutaconic acid; a methionine-loading test led to significant increase of both metabolites. In the skin fibrobla sts the activity of 3-methylglutaconyl-CoA hydratase was essentially normal . No explanation of this uncommon association of hypermethioninaemia and gl utaconic aciduria is available. The possibility of a common transporter for 3-methylglutaconic acid and methionine is an attractive hypothesis.