Reduction of large neutral amino acid concentrations in plasma and CSF of patients with maple syrup urine disease during crises

Neurological dysfunction is common in patients with maple syrup urine disea se (MSUD). However, the mechanisms underlying the neuropathology of this di sorder are poorly understood. We determined the concentrations of all amino acids in plasma of patients with MSUD during crises (with severe CNS sympt oms) and after recovery in the hope of detecting possible alterations of th ese levels during metabolic decompensation. Blood samples obtained from 11 children with MSUD aged 1 month to 7 years and from 10 age-matched controls (5 months to 6 years) with no evidence of metabolic disease were examined for their amino acid content by high-performance liquid chromatography. We observed that leucine, isoleucine and valine concentrations were respective ly 30, 9 and 3 times higher than normal values, whereas the concentrations of the large neutral amino acids (LNAA) phenylalanine, tyrosine, tryptophan and methionine were significantly lower during metabolic decompensation as compared to the controls. In addition, concentrations of leucine, but not of valine or isoleucine, were inversely related to the LNAA concentrations in plasma. The concentrations of these amino acids in plasma returned to no rmal values when patients were clinically well. CSF amino acid concentratio ns also showed decreased amounts of LNAA and increased concentrations of br anched-chain amino acids. It is possible that the decrease in plasma concen trations of LNAA may lead to a deficit of these essential amino acids in th e brain as well as of their products such as proteins and neurotransmitters , a fact that might be related to the neurological dysfunction of MSUD.