Inborn errors of metabolism in the maritimes, with special reference to maple-syrup-urine disease and Fabry's disease

Abstract Background: Maple 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 PCR and sequencing. Results: Nine new variants predicted as pathogenic were found between 30 variants identified in the 21 patients analyzed: two in the BCKDHA gene (p.Gly56Arg, and 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 four variants showed no pathogenicity according to in silico analysis. Conclusion: Given 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. Keywords: inborn errors of metabolism; maple syrup urine disease; branched-chain amino acids; valine; leucine; isoleucine.

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Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0096 ◽

2016 ◽

Vol 29 (10) ◽

Cited By ~ 4

Author(s):

Maryam Abiri ◽

Saeed Talebi ◽

Jouni Uitto ◽

Leila Youssefian ◽

Hassan Vahidnezhad ◽

...

Keyword(s):

Maple Syrup Urine Disease ◽

Autosomal Recessive ◽

Sandhoff Disease ◽

Compound Heterozygous ◽

Inborn Errors ◽

Maple Syrup ◽

Cherry Red Spot ◽

Urine Disease ◽

Autosomal Recessive Manner

AbstractMost inborn errors of metabolism (IEMs) are inherited in an autosomal recessive manner. IEMs are one of the major concerns in Iran due to its extensive consanguineous marriages. Herein, we report two patients with two co-existent IEMs: a girl affected by classic phenylketonuria (PKU) and maple syrup urine disease (MSUD) and a male patient affected with Sandhoff disease and PKU, where Sandhoff disease was suspected due to the presence of a cherry-red spot in the eyes at 6 months which is unrelated to PKU. Sequencing of candidate genes in the first patient revealed one novel and three recurrent compound heterozygous mutations of p.Ser231Pro and p.Ala300Ser in the

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Identification of Four New Mutations in Chilean Patients with Various Forms of Maple Syrup Urine Disease and Genotype-Phenotype Correlations

10.21203/rs.2.18080/v1 ◽

2019 ◽

Author(s):

Diana Ruffato Resende Campanholi ◽

Ana Vitoria Barban Margutti ◽

Wilson Araújo Silva ◽

Daniel Fantozzi Garcia ◽

Greice Andreotti de Molfetta ◽

...

Keyword(s):

Maple Syrup Urine Disease ◽

Point Mutations ◽

Cross Sectional Study ◽

Inborn Errors ◽

Cross Sectional ◽

Maple Syrup ◽

Pathogenic Mutations ◽

Genes Encoding ◽

Urine Disease ◽

Branched Chain

Abstract Background: Maple 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 four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes in a cohort of Chilean MSUD patients, and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 18 MSUD patients was carried out using PCR and DNA sequencing. Results: Four new pathogenic mutations were identified in the 18 patients that were analyzed: one in BCKDHA (p.Thr338Ile); two in BCKDHB (p.Gly336Ser e p.Pro240Thr); and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in the analyzed patients have been described previously. Conclusion: There were no correlations observed between genotypes and phenotypes. Thus, if MSUD is diagnosed more promptly, such as in neonatal screening, it might be possible to establish genotype-phenotype relationships more efficiently. Keywords: inborn errors of metabolism; maple syrup urine disease; branched-chain amino acids; valine; leucine; isoleucine.

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