Treatment of the acute crisis in maple syrup urine disease

Abstract

Background: The acute crisis of metabolic decompensation in maple syrup urine disease is a potentially lethal medical emergency that requires reduction in concentrations of leucine and other branched-chain amino acids in plasma. Experience with intravenous mixtures of amino acids indicates that this can be accomplished by the synthetic forces of protein synthesis. However, these intravenous mixtures are not generally available. Objective: To develop enteral mixtures suitable for administration by nasogastric drip in minimal volume. Design: Mixtures of amino acids were designed containing no leucine, isoleucine, or valine for administration by nasogastric drip. Needs for water and calories were to be met intravenously. They were designed to be used in the management of the acute crisis. Settings: Inpatient pediatric service. Patients: Two patients with maple syrup urine disease. Data were collected during the management of 3 episodes of metabolic imbalance. Intervention: Studies were carried out for 4 to 11 days, during which there was no intake of leucine. Four different mixtures were used and a fifth was designed on the basis of this experience. Main Outcome Measures: Effects on the concentrations of leucine and the other branched-chain amino acids. Clinical status closely mirrored the concentration of leucine. Results: In each instance, a progressive fall in leucine concentration was obtained. Rates of fall were comparable to those obtained with intravenous therapy. Concentrations of isoleucine fell to levels that made this amino acid limiting for protein synthesis and hence therapeutic effect. This led to greater and earlier supplementation with isoleucine. Valine supplementation was also useful. Conclusions: The acute crisis of metabolic imbalance in maple syrup urine disease may be effectively treated by the continuous intragastric drip of solutions of amino acids devoid of leucine along with provision of water and calories intravenously.