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Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branched-chain amino acids and thei...

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Autores principales: Liu, Yi-Dan, Chu, Xu, Liu, Rui-Hua, Sun, Ying, Kong, Qing-Xia, Li, Qiu-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522870/
https://www.ncbi.nlm.nih.gov/pubmed/30957186
http://dx.doi.org/10.3892/mmr.2019.10133
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author Liu, Yi-Dan
Chu, Xu
Liu, Rui-Hua
Sun, Ying
Kong, Qing-Xia
Li, Qiu-Bo
author_facet Liu, Yi-Dan
Chu, Xu
Liu, Rui-Hua
Sun, Ying
Kong, Qing-Xia
Li, Qiu-Bo
author_sort Liu, Yi-Dan
collection PubMed
description Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branched-chain amino acids and their corresponding branched-chain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become life-threatening. An 11-day-old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Of note, his 10-year-old sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. Genetic screening was performed, and the boy and his sister exhibited two novel compound heterozygous mutations in the branched chain keto acid dehydrogenase E1 subunit β (BCKDHB) gene: A substitution from guanine to adenine in the coding region at position 1,076 (c.1,076G>A) in exon 10 and a deletion of a thymine at position 705 (c.705delT) in exon 6. The missense mutation c.1076G>A results in an amino acid substitution from arginine to lysine at position 359 (p.Arg359Lys), whereas the mutation c.705delT results in the replacement of a cysteine at position 235 with a stop codon (p.Cys235Ter). Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1β subunits, resulting in a possible impairment of the activity of the BCKD complex. In the present study, it was hypothesized that the two novel heterozygous mutations in the BCKDHB gene found in the Chinese family may be responsible for the phenotype of the two siblings with MSUD.
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spelling pubmed-65228702019-06-18 Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease Liu, Yi-Dan Chu, Xu Liu, Rui-Hua Sun, Ying Kong, Qing-Xia Li, Qiu-Bo Mol Med Rep Articles Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branched-chain amino acids and their corresponding branched-chain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become life-threatening. An 11-day-old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Of note, his 10-year-old sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. Genetic screening was performed, and the boy and his sister exhibited two novel compound heterozygous mutations in the branched chain keto acid dehydrogenase E1 subunit β (BCKDHB) gene: A substitution from guanine to adenine in the coding region at position 1,076 (c.1,076G>A) in exon 10 and a deletion of a thymine at position 705 (c.705delT) in exon 6. The missense mutation c.1076G>A results in an amino acid substitution from arginine to lysine at position 359 (p.Arg359Lys), whereas the mutation c.705delT results in the replacement of a cysteine at position 235 with a stop codon (p.Cys235Ter). Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1β subunits, resulting in a possible impairment of the activity of the BCKD complex. In the present study, it was hypothesized that the two novel heterozygous mutations in the BCKDHB gene found in the Chinese family may be responsible for the phenotype of the two siblings with MSUD. D.A. Spandidos 2019-06 2019-04-05 /pmc/articles/PMC6522870/ /pubmed/30957186 http://dx.doi.org/10.3892/mmr.2019.10133 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Liu, Yi-Dan
Chu, Xu
Liu, Rui-Hua
Sun, Ying
Kong, Qing-Xia
Li, Qiu-Bo
Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title_full Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title_fullStr Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title_full_unstemmed Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title_short Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
title_sort paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522870/
https://www.ncbi.nlm.nih.gov/pubmed/30957186
http://dx.doi.org/10.3892/mmr.2019.10133
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