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Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity

  • Margutti, Ana Vitoria Barban1
  • Silva, Wilson Araújo Jr.2, 3, 2
  • Garcia, Daniel Fantozzi2, 3
  • de Molfetta, Greice Andreotti2, 3, 2
  • Marques, Adriana Aparecida3
  • Amorim, Tatiana4, 5
  • Prazeres, Vânia Mesquita Gadelha6
  • Boy da Silva, Raquel Tavares7
  • Miura, Irene Kazue8
  • Seda Neto, João8
  • Santos, Emerson de Santana9
  • Santos, Mara Lúcia Schmitz Ferreira10
  • Lourenço, Charles Marques11
  • Tonon, Tássia12
  • Sperb-Ludwig, Fernanda12, 13
  • de Souza, Carolina Fischinger Moura12
  • Schwartz, Ida Vanessa Döederlein12
  • Camelo, José Simon Jr.1
  • 1 University of São Paulo, Bandeirantes Av., 3900 – HC Criança - off D506, Ribeirão Prêto, SP, 14049-900, Brazil , Ribeirão Prêto (Brazil)
  • 2 University of São Paulo, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 3 National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 4 Associação de Pais e Amigos dos Excepcionais of Salvador, Salvador, BA, Brazil , Salvador (Brazil)
  • 5 Bahia State University, Salvador, BA, Brazil , Salvador (Brazil)
  • 6 Federal University of Amazonas, Manaus, AM, Brazil , Manaus (Brazil)
  • 7 Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil , Rio de Janeiro (Brazil)
  • 8 Sírio-Libanês Hospital, São Paulo, SP, Brazil , São Paulo (Brazil)
  • 9 Federal University of Sergipe, São Cristóvão, SE, Brazil , São Cristóvão (Brazil)
  • 10 Pequeno Príncipe Hospital, Curitiba, PR, Brazil , Curitiba (Brazil)
  • 11 Estácio University Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil , Ribeirão Preto (Brazil)
  • 12 Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil , Porto Alegre (Brazil)
  • 13 Clinics Hospital of Porto Alegre, Porto Alegre, RS, Brazil , Porto Alegre (Brazil)
Published Article
Orphanet Journal of Rare Diseases
Springer (Biomed Central Ltd.)
Publication Date
Nov 01, 2020
DOI: 10.1186/s13023-020-01590-7
Springer Nature


BackgroundMaple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing.ResultsEight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis.ConclusionGiven that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

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