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José Simon Camelo Junior
Universidade de Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4555-7633
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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.
Keywords
inborn errors of metabolism, maple syrup urine disease, branched-chain amino acids, valine, leucine, isoleucine
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
José Simon Camelo Junior
Universidade de Sao Paulo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4555-7633
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Complete author information
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History
CURRENT STATUS: Posted
The most recent version of this article is available here.
No community comments so far
Version 1
Posted 03 Dec, 2019
No comments provided
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Comments: 0
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Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
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.
Figure 1
Figure 2
Figure 3
Figure 4
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