maple syrup urine disease

Summary

Summary: An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids (AMINO ACIDS, BRANCHED-CHAIN). These metabolites accumulate in body fluids and render a "maple syrup" odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. (From Adams et al., Principles of Neurology, 6th ed, p936)

Top Publications

  1. Wu J, Kao H, Li S, Stevens R, Hillman S, Millington D, et al. ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease. J Clin Invest. 2004;113:434-40 pubmed
    ..of blood branched-chain amino acids (BCAAs), ketoaciduria, and clinical features resembling human maple syrup urine disease (MSUD), a severe genetic metabolic disorder caused by the deficiency of branched-chain alpha-keto acid ..
  2. Simon E, Schwarz M, Wendel U. Social outcome in adults with maple syrup urine disease (MSUD). J Inherit Metab Dis. 2007;30:264 pubmed
    ..Particular care must be exercised in the treatment of migrant patients who offer special problems due to cultural peculiarities and language difficulties. ..
  3. Edelmann L, Wasserstein M, Kornreich R, Sansaricq C, Snyderman S, Diaz G. Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001;69:863-8 pubmed
    b>Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of branched-chain amino acid metabolism...
  4. Jan W, Zimmerman R, Wang Z, Berry G, Kaplan P, Kaye E. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology. 2003;45:393-9 pubmed
    b>Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated...
  5. Chuang D, Chuang J, Wynn R. Lessons from genetic disorders of branched-chain amino acid metabolism. J Nutr. 2006;136:243S-9S pubmed publisher
    ..mutations in the mitochondrial branched-chain alpha-keto acid dehydrogenase complex (BCKDC) results in Maple Syrup Urine Disease (MSUD) or branched-chain ketoaciduria. There are presently five known clinical phenotypes for MSUD, i.e...
  6. Morton D, Strauss K, Robinson D, Puffenberger E, Kelley R. Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics. 2002;109:999-1008 pubmed
  7. Packman W, Mehta I, Rafie S, Mehta J, Naldi M, Mooney K. Young adults with MSUD and their transition to adulthood: psychosocial issues. J Genet Couns. 2012;21:692-703 pubmed publisher
    b>Maple Syrup Urine Disease (MSUD) is an autosomal recessive condition with an incidence of 1 in 185,000 births worldwide...
  8. Skvorak K, Hager E, Arning E, Bottiglieri T, Paul H, Strom S, et al. Hepatocyte transplantation (HTx) corrects selected neurometabolic abnormalities in murine intermediate maple syrup urine disease (iMSUD). Biochim Biophys Acta. 2009;1792:1004-10 pubmed publisher
  9. Barschak A, Sitta A, Deon M, de Oliveira M, Haeser A, Dutra Filho C, et al. Evidence that oxidative stress is increased in plasma from patients with maple syrup urine disease. Metab Brain Dis. 2006;21:279-86 pubmed
    b>Maple syrup urine disease (MSUD) or branched-chain alpha-keto aciduria (BCKA) is an inherited disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD) activity...

More Information

Publications68

  1. Ha J, Kim T, Eun B, Lee H, Lee K, Seol H, et al. Maple syrup urine disease encephalopathy: a follow-up study in the acute stage using diffusion-weighted MRI. Pediatr Radiol. 2004;34:163-6 pubmed
    Neonatal maple syrup urine disease (MSUD) is associated with diffuse oedema and characteristic MSUD oedema. We present a newborn infant with two coexisting different types of oedema...
  2. Skvorak K, Paul H, Dorko K, Marongiu F, Ellis E, Chace D, et al. Hepatocyte transplantation improves phenotype and extends survival in a murine model of intermediate maple syrup urine disease. Mol Ther. 2009;17:1266-73 pubmed publisher
    b>Maple syrup urine disease (MSUD; OMIM 248600) is an inborn error of metabolism of the branched chain alpha-ketoacid dehydrogenase (BCKDH) complex that is treated primarily by dietary manipulation of branched-chain amino acids (BCAA)...
  3. Coitinho A, de Mello C, Lima T, de Bastiani J, Fighera M, Wajner M. Pharmacological evidence that alpha-ketoisovaleric acid induces convulsions through GABAergic and glutamatergic mechanisms in rats. Brain Res. 2001;894:68-73 pubmed
    Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the pathophysiology of this disorder are poorly known...
  4. Araujo P, Wassermann G, Tallini K, Furlanetto V, Vargas C, Wannmacher C, et al. Reduction of large neutral amino acid levels in plasma and brain of hyperleucinemic rats. Neurochem Int. 2001;38:529-37 pubmed
    Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of this disorder are poorly known...
  5. Packman W, Henderson S, Mehta I, Ronen R, DANNER D, Chesterman B, et al. Psychosocial issues in families affected by maple syrup urine disease. J Genet Couns. 2007;16:799-809 pubmed
    The primary aim of this study was to ascertain the psychosocial issues faced by families affected by maple syrup urine disease (MSUD). The psychosocial adjustment and quality of life of children with MSUD were also described...
  6. Harris R, Zhang B, Goodwin G, Kuntz M, Shimomura Y, Rougraff P, et al. Regulation of the branched-chain alpha-ketoacid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease. Adv Enzyme Regul. 1990;30:245-63 pubmed
    ..b>Maple syrup urine disease is caused by an inherited deficiency in the branched-chain alpha-ketoacid dehydrogenase complex...
  7. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Luhovyy B, et al. Brain amino acid requirements and toxicity: the example of leucine. J Nutr. 2005;135:1531S-8S pubmed publisher
    ..In maple syrup urine disease, or a congenital deficiency of branched-chain ketoacid dehydrogenase, the brain concentration of KIC and ..
  8. Schonberger S, Schweiger B, Schwahn B, Schwarz M, Wendel U. Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease. Mol Genet Metab. 2004;82:69-75 pubmed
    b>Maple syrup urine disease (MSUD) is associated with increased branched-chain amino acids (BCAA), their keto acids (BCKA), and acute or chronic encephalopathy...
  9. Homanics G, Skvorak K, Ferguson C, Watkins S, Paul H. Production and characterization of murine models of classic and intermediate maple syrup urine disease. BMC Med Genet. 2006;7:33 pubmed
    b>Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has several clinical phenotypes depending on the degree of enzyme deficiency...
  10. Funchal C, Tramontina F, Quincozes dos Santos A, Fraga de Souza D, Goncalves C, Pessoa Pureur R, et al. Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells. J Neurol Sci. 2007;260:87-94 pubmed
    ..acids (BCAA) occurs in tissues and biological fluids of patients affected by the neurometabolic disorder maple syrup urine disease (MSUD)...
  11. Brunetti Pierri N, Lanpher B, Erez A, Ananieva E, Islam M, Marini J, et al. Phenylbutyrate therapy for maple syrup urine disease. Hum Mol Genet. 2011;20:631-40 pubmed publisher
    ..and their corresponding ?-keto acids (BCKA) in patients with classic and variant late-onset forms of maple syrup urine disease (MSUD). We also performed in vitro and in vivo experiments to elucidate the mechanism for this effect...
  12. Mitsubuchi H, Owada M, Endo F. Markers associated with inborn errors of metabolism of branched-chain amino acids and their relevance to upper levels of intake in healthy people: an implication from clinical and molecular investigations on maple syrup urine disease. J Nutr. 2005;135:1565S-70S pubmed publisher
    b>Maple syrup urine disease (MSUD) is caused by a deficiency in the branched-chain alpha-ketoacid dehydrogenase complex...
  13. Nobukuni Y, Mitsubuchi H, Akaboshi I, Indo Y, Endo F, Yoshioka A, et al. Maple syrup urine disease. Complete defect of the E1 beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the dis. J Clin Invest. 1991;87:1862-6 pubmed
    Branched chain alpha-ketoacid dehydrogenase (BCKDH) deficiency results in maple syrup urine disease (MSUD)...
  14. Muelly E, Moore G, Bunce S, Mack J, Bigler D, Morton D, et al. Biochemical correlates of neuropsychiatric illness in maple syrup urine disease. J Clin Invest. 2013;123:1809-20 pubmed publisher
    b>Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances...
  15. Aevarsson A, Chuang J, Wynn R, Turley S, Chuang D, Hol W. Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure. 2000;8:277-91 pubmed
    ..dehydrogenase multienzyme complexes can lead to serious and often fatal disorders in humans, including maple syrup urine disease (MSUD)...
  16. Righini A, Ramenghi L, Parini R, Triulzi F, Mosca F. Water apparent diffusion coefficient and T2 changes in the acute stage of maple syrup urine disease: evidence of intramyelinic and vasogenic-interstitial edema. J Neuroimaging. 2003;13:162-5 pubmed
    The acute phase of the neonatal classical form of maple syrup urine disease (MSUD) is usually associated with generalized brain edema.
  17. Sener R. Maple syrup urine disease: diffusion MRI, and proton MR spectroscopy findings. Comput Med Imaging Graph. 2007;31:106-10 pubmed
    A 7-month-old boy is reported with acute metabolic crisis of maple syrup urine disease. A reversible intramyelinic type of edema was noted by diffusion MRI which completely resolved in 3 months in accordance with good clinical outcome...
  18. Skvorak K, Dorko K, Marongiu F, Tahan V, Hansel M, Gramignoli R, et al. Improved amino acid, bioenergetic metabolite and neurotransmitter profiles following human amnion epithelial cell transplant in intermediate maple syrup urine disease mice. Mol Genet Metab. 2013;109:132-8 pubmed publisher
    Orthotopic liver transplant (OLT) significantly improves patient outcomes in maple syrup urine disease (MSUD; OMIM: 248600), yet organ shortages point to the need for alternative therapies...
  19. Carecchio M, Schneider S, Chan H, Lachmann R, Lee P, Murphy E, et al. Movement disorders in adult surviving patients with maple syrup urine disease. Mov Disord. 2011;26:1324-8 pubmed publisher
    b>Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched-chain ?-keto acid dehydrogenase complex gene...
  20. Mescka C, Moraes T, Rosa A, Mazzola P, Piccoli B, Jacques C, et al. In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease. Metab Brain Dis. 2011;26:21-8 pubmed publisher
    b>Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain ?-keto acid dehydrogenase (BCKAD) leading to accumulation of ..
  21. Strauss K, Wardley B, Robinson D, Hendrickson C, Rider N, Puffenberger E, et al. Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab. 2010;99:333-45 pubmed publisher
    ..Treatment for classical maple syrup urine disease (MSUD) should address this underlying physiology while also protecting children from nutrient ..
  22. Bhattacharya K, Khalili V, Wiley V, Carpenter K, Wilcken B. Newborn screening may fail to identify intermediate forms of maple syrup urine disease. J Inherit Metab Dis. 2006;29:586 pubmed
    ..Metabolic diseases still need to be considered in appropriate clinical situations later in life...
  23. Wajner M, Coelho D, Barschak A, Araújo P, Pires R, Lulhier F, et al. Reduction of large neutral amino acid concentrations in plasma and CSF of patients with maple syrup urine disease during crises. J Inherit Metab Dis. 2000;23:505-12 pubmed
    Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of this disorder are poorly understood...
  24. Vasques V, Brinco F, Wajner M. Intrahippocampal administration of the branched-chain alpha-hydroxy acids accumulating in maple syrup urine disease compromises rat performance in aversive and non-aversive behavioral tasks. J Neurol Sci. 2005;232:11-21 pubmed
    b>Maple syrup urine disease (MSUD) is an inherited metabolic disease predominantly characterized by neurological dysfunction...
  25. Wynn R, Chuang J, Sansaricq C, Mandel H, Chuang D. Biochemical basis of type IB (E1beta ) mutations in maple syrup urine disease. A prevalent allele in patients from the Druze kindred in Israel. J Biol Chem. 2001;276:36550-6 pubmed
    b>Maple syrup urine disease (MSUD) is a metabolic disorder associated with often-fatal ketoacidosis, neurological derangement, and mental retardation...
  26. Funchal C, Dos Santos A, Jacques Silva M, Zamoner A, Gottfried C, Wajner M, et al. Branched-chain alpha-keto acids accumulating in maple syrup urine disease induce reorganization of phosphorylated GFAP in C6-glioma cells. Metab Brain Dis. 2005;20:205-17 pubmed
    ..alpha-ketoisovaleric (KIV), and alpha-keto-beta-methylvaleric (KMV) acids, metabolites accumulating in maple syrup urine disease (MSUD), on the in vitro phosphorylation of glial fibrillary acidic protein (GFAP) and cytoskeletal ..
  27. Fisher C, Lau K, Fisher C, Wynn R, Cox R, Chuang D. A 17-bp insertion and a Phe215----Cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34. Biochem Biophys Res Commun. 1991;174:804-9 pubmed
    ..The above results support the thesis that the thiamine-responsive MSUD patient (WG-34) is a compound heterozygote at the E2 locus. The implication of the E2 mutations for the thiamine-responsiveness observed in this patient is discussed...
  28. Oglesbee D, Sanders K, Lacey J, Magera M, Casetta B, Strauss K, et al. Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening for maple syrup urine disease (MSUD). Clin Chem. 2008;54:542-9 pubmed publisher
    Newborn screening for maple syrup urine disease (MSUD) relies on finding increased concentrations of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine by tandem mass spectrometry (MS/MS)...
  29. Flaschker N, Feyen O, Fend S, Simon E, Schadewaldt P, Wendel U. Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. J Inherit Metab Dis. 2007;30:903-9 pubmed
    In maple syrup urine disease (MSUD), disease-causing mutations can affect the BCKDHA, BCKDHB or DBT genes encoding for the E1 alpha, E1 beta and E2 subunits of the multienzyme branched-chain 2-keto acid dehydrogenase (BCKD) complex.
  30. Sener R. Diffusion magnetic resonance imaging in intermediate form of maple syrup urine disease. J Neuroimaging. 2002;12:368-70 pubmed
    An 8-year-old boy with the intermediate variant of maple syrup urine disease is reported...
  31. Jouvet P, Jugie M, Rabier D, Desgres J, Hubert P, Saudubray J, et al. Combined nutritional support and continuous extracorporeal removal therapy in the severe acute phase of maple syrup urine disease. Intensive Care Med. 2001;27:1798-806 pubmed
    The authors assessed the efficiency, tolerance and outcome of neonates and children with maple syrup urine disease (MSUD) in acute decompensation managed by endogenous and extracorporeal removal of accumulated MSUD metabolites.
  32. Mazariegos G, Morton D, Sindhi R, Soltys K, Nayyar N, Bond G, et al. Liver transplantation for classical maple syrup urine disease: long-term follow-up in 37 patients and comparative United Network for Organ Sharing experience. J Pediatr. 2012;160:116-21.e1 pubmed publisher
    To assess clinical and neurocognitive function in children who have undergone liver transplantation for classical maple syrup urine disease (MSUD).
  33. Wynn R, Davie J, Chuang J, Cote C, Chuang D. Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease. J Biol Chem. 1998;273:13110-8 pubmed
    ..5 kDa) and two E1beta (37.5 kDa) subunits forming an alpha2 beta2 tetramer. In patients with type IA maple syrup urine disease, the E1alpha subunit is affected, resulting in the loss of E1 and branched-chain ketoacid dehydrogenase ..
  34. Chuang J, Wynn R, Moss C, Song J, Li J, Awad N, et al. Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype. J Biol Chem. 2004;279:17792-800 pubmed
    b>Maple syrup urine disease (MSUD) results from mutations affecting different subunits of the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex...
  35. Le Roux C, Murphy E, Hallam P, Lilburn M, Orlowska D, Lee P. Neuropsychometric outcome predictors for adults with maple syrup urine disease. J Inherit Metab Dis. 2006;29:201-2 pubmed
    ..We describe 14 adult MSUD patients (3 with intermediate MSUD) with varied clinical and neuropsychometric outcomes. Age at diagnosis appears to be a predictor of IQ even in adults, while long-term blood leucine does not correlate with IQ...
  36. Funchal C, Gottfried C, de Almeida L, Wajner M, Pessoa Pureur R. Evidence that the branched-chain alpha-keto acids accumulating in maple syrup urine disease induce morphological alterations and death in cultured astrocytes from rat cerebral cortex. Glia. 2004;48:230-40 pubmed
    ..symptoms, cerebral edema, and atrophy are common features of the inherited metabolic disorder maple syrup urine disease (MSUD)...
  37. Oyarzabal A, Martinez Pardo M, Merinero B, Navarrete R, Desviat L, Ugarte M, et al. A novel regulatory defect in the branched-chain ?-keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease. Hum Mutat. 2013;34:355-62 pubmed publisher
    ..PP2Cm, a recently described member of the branched-chain ?-keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD)...
  38. Healy P, Dennis J, Windsor P, Pierce K, Schofield P. Genotyping cattle for inherited congenital myoclonus and maple syrup urine disease. Aust Vet J. 2002;80:695-7 pubmed
    ..a routine procedure for establishing the inherited congenital myoclonus (ICM) genotype of cattle and to obtain an estimate of the prevalence of heterozygotes for ICM and maple syrup urine disease (MSUD) in Australian Poll Herefords.
  39. Schadewaldt P, Bodner Leidecker A, Hammen H, Wendel U. Significance of L-alloisoleucine in plasma for diagnosis of maple syrup urine disease. Clin Chem. 1999;45:1734-40 pubmed
    The significance of plasma L-alloisoleucine, which is derived from L-isoleucine in vivo, for diagnosis of maple syrup urine disease (MSUD) was examined.
  40. Bridi R, Braun C, Zorzi G, Wannmacher C, Wajner M, Lissi E, et al. alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. Metab Brain Dis. 2005;20:155-67 pubmed
    b>Maple syrup urine disease (MSUD) is an inherited neurometabolic disorder caused by deficiency of branched-chain alpha-keto acid dehydrogenase complex activity which leads to tissue accumulation of the branched-chain alpha-keto acids (..
  41. Fisher C, Fisher C, Chuang J, Lau K, Chuang D, Cox R. Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple-exon skipping as a secondary effect of the mutations. Am J Hum Genet. 1993;52:414-24 pubmed
    ..gene of the human branched-chain alpha-keto acid dehydrogenase (BCKAD) complex in 6 of 38 patients with maple syrup urine disease (MSUD)...
  42. Bridi R, Araldi J, Sgarbi M, Testa C, Durigon K, Wajner M, et al. Induction of oxidative stress in rat brain by the metabolites accumulating in maple syrup urine disease. Int J Dev Neurosci. 2003;21:327-32 pubmed
    b>Maple syrup urine disease (MSUD) is an inherited disorder caused by deficiency of branched-chain L-2-keto acid dehydrogenase complex activity...
  43. Barschak A, Marchesan C, Sitta A, Deon M, Giugliani R, Wajner M, et al. Maple syrup urine disease in treated patients: biochemical and oxidative stress profiles. Clin Biochem. 2008;41:317-24 pubmed
    ..The objective of this study was to evaluate and correlate the biochemical and oxidative stress profiles in MSUD patients during the dietary treatment...
  44. Zhang B, Edenberg H, Crabb D, Harris R. Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease. J Clin Invest. 1989;83:1425-9 pubmed
    b>Maple syrup urine disease (MSUD) results from a deficiency of branched chain alpha-ketoacid dehydrogenase (BCKDH)...
  45. Scaini G, Teodorak B, Jeremias I, Morais M, Mina F, Dominguini D, et al. Antioxidant administration prevents memory impairment in an animal model of maple syrup urine disease. Behav Brain Res. 2012;231:92-6 pubmed publisher
    b>Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder resulting from deficiency of branched-chain ?-keto acid dehydrogenase complex leading to branched chain amino acids (BCAA) leucine, isoleucine, and valine ..
  46. Sgaravatti A, Rosa R, Schuck P, Ribeiro C, Wannmacher C, Wyse A, et al. Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta. 2003;1639:232-8 pubmed
    Neurological dysfunction is a common finding in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly known...
  47. Tsuruta M, Mitsubuchi H, Mardy S, Miura Y, Hayashida Y, Kinugasa A, et al. Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain alpha-keto acid dehydrogenase complex. J Hum Genet. 1998;43:91-100 pubmed
    ..dehydrogenase (BCKDH) complex was studied at the molecular level in three patients with intermittent maple syrup urine disease (MSUD). All three patients had higher BCKDH activity than did those with the classical phenotype...
  48. Simon E, Flaschker N, Schadewaldt P, Langenbeck U, Wendel U. Variant maple syrup urine disease (MSUD)--the entire spectrum. J Inherit Metab Dis. 2006;29:716-24 pubmed
    In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched-chain amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction...
  49. Hmiel S, Martin R, Landt M, Levy F, Grange D. Amino acid clearance during acute metabolic decompensation in maple syrup urine disease treated with continuous venovenous hemodialysis with filtration. Pediatr Crit Care Med. 2004;5:278-81 pubmed
    Assessment of amino acid clearances by continuous venovenous hemodialysis with filtration in treatment of a metabolic decompensation in acute maple syrup urine disease.
  50. Strauss K, Mazariegos G, Sindhi R, Squires R, Finegold D, Vockley G, et al. Elective liver transplantation for the treatment of classical maple syrup urine disease. Am J Transplant. 2006;6:557-64 pubmed
    An 8.5-year-old girl with classical maple syrup urine disease (MSUD) required liver transplantation for hypervitaminosis A and was effectively cured of MSUD over an 8-year clinical follow-up period...
  51. Nellis M, Danner D. Gene preference in maple syrup urine disease. Am J Hum Genet. 2001;68:232-7 pubmed
    Untreated maple syrup urine disease (MSUD) results in mental and physical disabilities and often leads to neonatal death...
  52. Zinnanti W, Lazovic J, Griffin K, Skvorak K, Paul H, Homanics G, et al. Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease. Brain. 2009;132:903-18 pubmed publisher
    b>Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with life-threatening cerebral oedema and dysmyelination in affected individuals...
  53. Skvorak K. Animal models of maple syrup urine disease. J Inherit Metab Dis. 2009;32:229-46 pubmed publisher
    b>Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase (BCKDH) complex...
  54. Walsh K, Scott M. Neurocognitive profile in a case of maple syrup urine disease. Clin Neuropsychol. 2010;24:689-700 pubmed publisher
    b>Maple Syrup Urine Disease (MSUD) is a metabolic disease with associated enzyme deficiency and an inability to break down amino acids. Neurotoxic levels can occur resulting in neurological sequelae...
  55. Shellmer D, DeVito Dabbs A, Dew M, Noll R, Feldman H, Strauss K, et al. Cognitive and adaptive functioning after liver transplantation for maple syrup urine disease: a case series. Pediatr Transplant. 2011;15:58-64 pubmed publisher
    ..In general, findings indicate that liver transplantation minimizes the likelihood of additional central nervous system damage, providing an opportunity for possible stabilization or improvement in neurocognitive functioning...
  56. Patel M. Inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in developing rat and human brain. Biochem J. 1974;144:91-7 pubmed
  57. Jouvet P, Rustin P, Taylor D, Pocock J, Felderhoff Mueser U, Mazarakis N, et al. Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease. Mol Biol Cell. 2000;11:1919-32 pubmed
    b>Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants...
  58. Khanna A, Hart M, Nyhan W, Hassanein T, Panyard Davis J, Barshop B. Domino liver transplantation in maple syrup urine disease. Liver Transpl. 2006;12:876-82 pubmed
    Liver transplantation has been reported in a few cases of maple syrup urine disease (MSUD), but is controversial. Many patients with approved indications for liver transplantation die before grafts are available...
  59. Song J, Chuang D. Natural osmolyte trimethylamine N-oxide corrects assembly defects of mutant branched-chain alpha-ketoacid decarboxylase in maple syrup urine disease. J Biol Chem. 2001;276:40241-6 pubmed
    b>Maple syrup urine disease is caused by deficiency in the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The clinical phenotype includes often fatal ketoacidosis, neurological derangement, and mental retardation...