Patients with maple syrup urine disease (MSUD), even mild variants, are at risk of encephalopathy when subjected to major metabolic stress. This disorder is widely regarded as very rare but this may not be so. Our recent experience suggests that the mild variants may be difficult to diagnose and therefore easy to overlooked. During the episodes of decompensation plasma aminoacid profiles are abnormal, but these often rapidly return to normal with treatment. Between attacks plasma aminoacids are usually normal and the activity of the branched chain oxoacid (BCOA) decarboxylase complex in fibroblasts do not correlate well with the severity of the disease. Whole body leucine oxidation in vivo may provide better insight into the disorder.

We have studied two patients. One, a girl of 15 years, who presented at the age of 4 years with severe encephalopathy requiring intensive care (maximum plasma leucine 1600 μmol/l). Since then, on modest protein restriction, she has been well with no episodes of decompensation and normal plasma aminoacid concentrations. The second, a boy aged 8 years has had two episodes of encephalopathy with raised branched chain aminoacid concentrations but normal BCOA oxidation in cultured skin fibroblasts. Whole body leucine oxidation was measured using a continuous infusion of 1-13 C-leucine and was 5μmol/kg/h and 11 μmol/kg/h respectively, 31% and 68% of the reference values of children of similar age. Both these two patients remain at risk of decompensation, even as adults, and need to be given careful instructions to prevent serious illness.

We conclude that measurement of the whole body leucine oxidation establishes the diagnosis more reliably and gives a better assessment of the severity of the disorder than conventional investigations.