The progress of treatment must, therefore, be monitored frequently to determine when the branched-chain amino acids (isoleucine, valine, and ultimately leucine) must be added back to the diet. The concentrations of isoleucine and/or valine may become too low on this regimen and limit the rate of new protein synthesis.
#Maple syrup urine disease free#
The rationale for this treatment is to suppress protein catabolism (which will increase production of leucine and the other toxic branched-chain amino acids) and induce an anabolic state (which will stimulate de novo protein synthesis and thereby decrease the concentration of the free branched-chain amino acids). Treatment of an acutely ill newborn should include hypercaloric nutritional support that contains high concentrations of glucose (>10 mg/kg per minute) an insulin infusion (0.05-0.10 units/kg per hour) to avoid hyperglycemia and a leucine, isoleucine, and valine-free protein source (intravenous, if available, or enteral, using specially prepared formula).
#Maple syrup urine disease skin#
Definitive enzyme analysis can be performed with leukocytes or cultured skin fibroblasts, but treatment should not be delayed pending definitive diagnosis. Maple syrup urine disease is not associated with abnormal carnitine metabolism. The characteristic plasma amino acid findings are increased concentrations of leucine, isoleucine, valine, and allo-isoleucine (the presence of allo-isoleucine is pathognomonic for MSUD), and the characteristic urinary organic acid pattern (see Specialized Biochemical Testing). The diagnosis should then be established by plasma amino acid analysis and urine organic acid analysis. Once suspected, the diagnosis may be provisionally confirmed by a rapid screening test, the dinitrophenylhydrazine (DNPH) test, which detects the α-ketoacids that are formed from the isoleucine, leucine, and valine (see Screening Studies under Biochemical Testing).
In either case, response to a positive screening result must be rapid.īedside detection of the characteristic odor of maple syrup by an alert parent or nurse might be the first clue to the diagnosis of this disorder. However, a positive newborn screening result might not be received until after the newborn has already become ill and is in the neonatal intensive care unit. The rate of false-positive and false-negative results has been reduced by the use of MS (mass spectrometry)/MS technology, which can concurrently measure the concentrations of isoleucine, leucine, and valine, thereby permitting the use of amino acid ratios to more reliably identify at-risk newborns. There are relatively few false-positive results for healthy full-term infants.
Newborn screening programs for MSUD are based on the detection of hyperleucinemia. If the patient recovers from this initial episode, the disorder can be characterized by growth failure, mental retardation, and recurrent episodes of metabolic decompensation. If untreated, however, it may lead to hypoglycemia and ketoacidosis. The disease does not generally produce metabolic acidosis, lactic acidemia, hypoglycemia, hyperammonemia, ketosis, or abnormal acylcarnitines. Patients with the severe neonatal form of MSUD are generally normal for the first 2 or 3 days of life but then develop lethargy, hypertonia with extreme opisthotonic posturing (even when unconscious), seizures, and progressive encephalopathy, which may lead to death. 116,138 The classical clinical variant of this disorder manifests in the neonatal period and can lead to serious consequences if it is not recognized and treated quickly (i.e., within the first week of life). Maple syrup urine disease is an inborn error of branched-chain amino acid metabolism caused by branched-chain α-ketoacid dehydrogenase deficiency, which impairs isoleucine, leucine, and valine metabolism. Martin MBBS, FRACP, in Fanaroff and Martin's Neonatal-Perinatal Medicine, 2020 Maple Syrup Urine Disease