Advances in the diagnosis and treatment of maple syrup urine disease: experience in Galicia (Spain)

INTRODUCTION: Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder caused by an inherited deficiency of branched chain alpha-ketoacid dehydrogenase activity. Accumulation of the amino acids leucine, isoleucine, valine and alloisoleucine and their metabolic products in cells and biological fluids results in severe brain dysfunction. PATIENTS AND METHODS: We present three cases of MSUD diagnosed in Galicia since 2000, the year in which the Extended Newborn Screening Program by tandem mass spectrometry was started in this region. One of the patients was diagnosed on the basis of early clinical presentation and the others by neonatal screening. Enzymatic and molecular studies confirmed two classic cases of MSUD and an intermediate variant. We describe the clinical and biochemical details at confirmation of diagnosis and the long-term outcome of the three patients. Throughout follow-up, all the patients maintained adequate leucine levels, which were near the normal range (mean levels: 220, 177 and 252 micromol/L, respectively). Several moderate metabolic decompensations were observed but leucine levels only occasionally exceeded 1000 micromol/L (one day in two patients). IQ tests were performed in all patients and scores were within the normal range. In view of our results, we believe the following measures are essential to improve the prognosis of MSUD: inclusion of this disease in Expanded Neonatal Screening Programs with early samples (at 2-3 days of life); aggressive treatment in the initial phase and during acute decompensations; strict metabolic control to prevent crises, monitoring of branched-chain amino acids (dried blood spot sample), and maintenance of long term plasma leucine levels below 300 micromol/L.