Disease relevance of Maple Syrup Urine Disease

• The need of essential amino acids in children. An evaluation based on the intake of phenylalanine, tyrosine, leucine, isoleucine, and valine in children with phenylketonuria, tyrosine amino transferase defect, and maple syrup urine disease [1].
• Glutamate and gamma-aminobutyric acid neurotransmitter systems in the acute phase of maple syrup urine disease and citrullinemia encephalopathies in newborn calves [2].
• Whole-body L-leucine oxidation was assessed in patients with maple syrup urine disease of different severity using oral L-[1-(13)C]leucine bolus tests (38 micromol/kg body weight) [3].
• Prolongation of G1 and S phase in C-6 glioma cells treated with maple syrup urine disease metabolits. Morphologic and cell cycle studies [4].
• Monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) activities have been measured in fibroblasts from nine healthy controls, three patients with maple syrup urine disease (MSUD) and six patients with Lesch-Nyhan syndrome [5].

High impact information on Maple Syrup Urine Disease

• Branched-chain amino acid-free parenteral nutrition in the treatment of acute metabolic decompensation in patients with maple syrup urine disease [6].
• Maple syrup urine disease (MSUD) or branched-chain alpha-ketoaciduria is an autosomally inherited disorder in the catabolism of branched-chain amino acids leucine, isoleucine, and valine [7].
• E2 transacylase-deficient (type II) maple syrup urine disease. Aberrant splicing of E2 mRNA caused by internal intronic deletions and association with thiamine-responsive phenotype [7].
• Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients [8].
• Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region [9].

Chemical compound and disease context of Maple Syrup Urine Disease

• Unexpectedly, 14CO2 production from [1-(14)C] leucine was partially depressed (80%) in isovaleric acidemia cells whereas in maple syrup urine disease cells it was strongly depressed (99%) as expected [10].
• Glucose and alanine metabolism in children with maple syrup urine disease [11].
• Radioactive isovaleric acid accumulated in assay media with isovaleric acidemia cells but not in those with maple syrup urine disease cells [10].
• Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate [12].
• On the mechanisms of the formation of L-alloisoleucine and the 2-hydroxy-3-methylvaleric acid stereoisomers from L-isoleucine in maple syrup urine disease patients and in normal humans [13].

Biological context of Maple Syrup Urine Disease

• Complementation of defective leucine decarboxylation in fibroblasts from a maple syrup urine disease patient by retrovirus-mediated gene transfer [14].
• Effect of insulin on leucine kinetics in maple syrup urine disease [15].
• Assessment of whole body L-leucine oxidation by noninvasive L-[1-13C]leucine breath tests: a reappraisal in patients with maple syrup urine disease, obligate heterozygotes, and healthy subjects [16].
• The maple syrup urine disease metabolites, i.e., L-leucine, L-isoleucine, and L-valine and their corresponding ketoacids caused a prolongation of the G1 and S phases, when administered in combination at concentrations corresponding to approximately the highest recorded plasma levels in patients with the disease (1 x level) [4].
• Seven infants diagnosed with methylmalonyl-CoA mutase deficiency (n=2), ornithine carbamoyltransferase deficiency (n=1), propionic acidaemia (n=1), isovaleric acidaemia (n=1), maple syrup urine disease (n=1) and glutaric acidemia type I (n=1) were tried with breastfeeding over two years [17].

Anatomical context of Maple Syrup Urine Disease

• The biochemical basis for the therapeutic effects of thiamin in thiamin-responsive maple-syrup-urine disease (MSUD) was investigated in intact and disrupted fibroblast cultures from normals and patients with various forms of MSUD [12].
• Control of pyruvate and beta-hydroxybutyrate utilization in rat brain mitochondria and its relevance to phenylketonuria and maple syrup urine disease [18].
• Inhibition, by 2-oxo acids that accumulate in maple-syrup-urine disease, of lactate, pyruvate, and 3-hydroxybutyrate transport across the blood-brain barrier [19].
• Cultured cells of normal individuals and nine patients with different clinical pictures of maple syrup urine disease (MSUD) are studied with both alpha-ketoisocaproic acid (2-oxo-4-methylpentanoic acid (KIC)) and alpha-ketoisovaleric acid (2-oxo-3-methylbutanoic acid (KIVA)) as substrates [20].
• Reduction of glutamate uptake into cerebral cortex of developing rats by the branched-chain alpha-keto acids accumulating in maple syrup urine disease [21].

Gene context of Maple Syrup Urine Disease

• We report the occurrence of three novel mutations in the E1 alpha (BCKDHA) locus of the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex that cause maple syrup urine disease (MSUD) [22].
• Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain alpha-keto acid dehydrogenase complex [23].
• Maple syrup urine disease: domain structure, mutations and exon skipping in the dihydrolipoyl transacylase (E2) component of the branched-chain alpha-keto acid dehydrogenase complex [24].
• Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex [25].
• Determinations performed with GDH, LDH A4 and LDH C4 allow differentiation of E3 deficiency from other clinical phenotypes of maple syrup urine disease [26].

References