Nutrition management guideline for maple syrup urine disease: An evidence- and consensus-based approach (original) (raw)
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Journal of Evaluation in Clinical Practice, 2013
The management of many inherited metabolic disorders (IMDs) is dependent on nutrition intervention, but few clinical management guidelines for these uncommon disorders exist. Clinicians are forced to make nutrition treatment decisions using limited data. This results in clinical variations in both service and cost. We describe a method for establishing management guidelines to help clinicians treat patients with IMDs. Methods The Southeast Newborn Screening and Genetics Collaborative (Region 3) convened a group of nine national experts in metabolic nutrition to determine the pertinent issues in the development of nutrition management guidelines for IMDs. These experts were trained in evidence analysis and examined established consensus techniques for guideline development.
Healthcare
Maple syrup urine disease (MSUD) is a metabolic disorder characterized by a difficulty to digest and process proteins necessary for growth. To monitor and maintain the ideal growth of children with MSUD, caregivers need to carefully control the consumption of harmful branched-chain amino acids (BCAAs). The dietary limits of amino acids for MSUD patients are recommended and controlled by pediatricians and metabolic dietitians according to age, height, weight, and the prevailing percentage of amino acids in the body. This study introduces an intelligent dietary tool called MSUD Baby Buddy for caregivers of MSUD patients that tracks the amino acids intake out of baby formulas for babies 0–6 months old. This tool aims to provide accurate recommendations of the appropriate daily intake of protein and BCAAs based on the patients’ data, plasma BCAAs, and formula preferences. We use a knowledge-based system, including knowledge acquisition and verification, as well as knowledge management t...
Maple syrup urine disease: An uncommon cause for neonatal metabolic distress
Indian journal of clinical biochemistry : IJCB, 1999
Maple Syrup Urine Disease is an autosomal recessive disorder caused by a deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex. This rare disorder represents one of the causes of acute neonatal illness which results in devastating disturbances of neurological development. On investigation of 1750 infants with neurological impairment for inborn errors of amino acid metabolism, 4 neonates with classical maple syrup urine disease were detected. These otherwise normal neonates presented in the first week after birth with seizures, lethargy and refusal of feeds, hypoglycemia and metabolic acidosis. The plasma and urine concentrations of the branched-chain amino acids were increased and there was ketoaciduria. Two of these neonates expired before specific treatment could be instituted. Routine biochemical screening of neonates with acute illness could unearth many cases of this rare inherited metabolic disease.
Molecular Genetics and Metabolism, 2013
A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.
Health and Quality of Life Outcomes, 2013
Introduction The development in therapeutic strategies has increased survival of children affected by inborn errors of metabolism with restricted diet (IEMRD). These diseases have mild- and long-term consequences on the health. Little is known about the impact on the quality of life (QoL) of children and their families. The aims of this study were: to compare the QoL of the children and parents affected by IEMRD with the QoL of the general population and one pathology associated with long-term consequences. Patients and methods This cross-sectional study was performed at the French Reference Center for inborn metabolic disorders (Marseille, France). Inclusion criteria were: a child with a diagnosis of organic aciduria, urea cycle defect, or maple syrups urine disease (MSUD). Socio-demographics, clinical data, and QoL were recorded. Results Twenty-one of 32 eligible families were included during a planned routine visit. Ten (47%, 95% CI 27-69%) children were affected by organic acidu...
Glucose and Alanine Metabolism in Children with Maple Syrup Urine Disease
Journal of Clinical Investigation, 1978
vitro studies have suggested that catabolism of branched chain amino acids is linked with alanine and glutamine formed in, and released from, muscle. To explore this possibility in vivo, static and kinetic studies were performed in three patients with classical, and one patient with partial, branched chain a-ketoacid decarboxylase deficiency (maple syrup urine disease, MSUD) and compared to similar studies in eight age-matched controls. The subjects underwent a 24-30-h fast, and a glucose-alanine flux study using stable isotopes. Basal plasma leucine concentrations were elevated (P < 0.001) in patients with MSUD (1,140+125 ,uM vs. 155±18 ,uM in controls); and in contrast to the controls, branched chain amino acid concentrations in plasma increased during the fast in the MSUD patients. Basal plasma alanine concentrations were lower (P < 0.01) in patients with classical MSUD (153±8 ,M vs. 495±27 uM in controls). This discrepancy was maintained throughout the fast despite a decrease in alanine concentrations in both groups. Plasma alanine and leucine concentrations in the patient with partial MSUD were intermediate between those of the controls and the subjects with the classical form of the disease. Circulating ketone bodies and glucoregulatory hormones concentrations were similar in the MSUD and normal subjects during the fast. Alanine flux rates in two patients with classical MSUD (3.76 and 4.00 ,umol/Kg per min) and the patient with partial MSUD (5.76 ,umol/Kg per min) were clearly lower than those ofthe controls (11.72±2.53 [SD] ,umol/ Kg per min). After short-term starvation, glucose flux and fasting concentrations were similar in the MSUD patients and normal subjects. These data indicate that branched chain amino acid
2020
Background Distinguishing systemic metabolic disruptions in maple syrup urine disease (MSUD) beyond amino acid pathways is under-investigated, yet important to understanding disease pathology and treatment options. Methods An adolescent female (15 years) with MSUD without liver transplant, attended 2 study visits, 5 days apart. Medical diet adherence was determined based on her 3-day diet records and plasma branched-chain amino acid (BCAA) concentrations at both study visits. Plasma from a single age- and sex-matched control (MURDOCK Study, Duke University) and the case patient were analyzed with UPLC/MS/MS for intensity (m/z), annotated, and normalized against a median of 1 (Metabolon, Morrisville NC). Differences between case/control and 5-day comparisons were defined as ≥ ǀ 0.5 ǀ. Results 434 lipid metabolites were identified across samples; 90 (20.7%) were higher and 120 (27.6%) lower in the MSUD case at baseline compared with control. By study visit 2, plasma BCAA had declined,...
International Journal of Neonatal Screening, 2021
Maple syrup urine disease is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase, responsible for degradation of leucine, isoleucine, and valine. Biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT genes result in enzyme deficiency. We report the case of a female infant who presented with mild gross motor delay at 4 months, and seizures with hypoglycaemia at 5 months. Newborn screening returned total leucine/isoleucine at the 99.5th centile of the population; however, as second-tier testing reported minimal alloisoleucine, the results were considered inconsistent with MSUD. Plasma amino acid and urine organic acid analyses at 5 months were, however, consistent with a diagnosis of MSUD. A brain MRI showed bilateral symmetrical T2 hyperintense signal abnormalities involving white matter, globus pallidus, thalamus, brainstem, and dentate nuclei with restricted diffusion. A repeat MRI 10 months post-dietary-intervention showed the resolution of these changes and pr...
Management of a Woman With Maple Syrup Urine Disease During Pregnancy, Delivery, and Lactation
Journal of Parenteral and Enteral Nutrition, 2014
Maple syrup urine disease (MSUD) (OMIM 248600) is an inherited disorder in metabolism of the branched-chain amino acids (BCAA), leucine, isoleucine, and valine, caused by deficient activity of one of the proteins in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). Plasma and urine concentrations of BCAA and allo-isoleucine are markedly increased, and their branched-chain ketoacid analogues appear in urine. The treatment for MSUD is a diet restricted in BCAA that controls these abnormalities. Metabolic crisis characterized by ketoacidosis can develop rapidly at any age, precipitated by catabolism due to intercurrent illness, surgery, or physiological stress, or by excessive intake of BCAA. The toxic metabolite is leucine. Leucine intoxication is associated with ketosis and the risk of cerebral edema and requires aggressive nutrition therapy using enteral or parenteral BCAA-free protein with high energy intake to promote removal of toxic metabolites, reduce catabolism, and promote anabolism, in effect promoting the net incorporation of BCAA into protein.