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Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II

Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydro...

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Autores principales: Zhu, Sijia, Ding, Dongxue, Jiang, Jianhua, Liu, Meirong, Yu, Liqiang, Fang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911658/
https://www.ncbi.nlm.nih.gov/pubmed/36779069
http://dx.doi.org/10.3389/fneur.2023.1087421
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author Zhu, Sijia
Ding, Dongxue
Jiang, Jianhua
Liu, Meirong
Yu, Liqiang
Fang, Qi
author_facet Zhu, Sijia
Ding, Dongxue
Jiang, Jianhua
Liu, Meirong
Yu, Liqiang
Fang, Qi
author_sort Zhu, Sijia
collection PubMed
description Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Thus far, the high clinical heterogeneity of late-onset GA II has brought a great challenge for its diagnosis. In this study, we reported a 21-year-old Chinese man with muscle weakness, vomiting, and severe pain. Muscle biopsy revealed myopathological patterns of lipid storage myopathy, and urine organic acid analyses showed a slight increase in glycolic acid. All the aforementioned results were consistent with GA II. Whole-exome sequencing (WES), followed by bioinformatics and structural analyses, revealed two compound heterozygous missense mutations: c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11, which were classified as “likely pathogenic” according to American College of Medical Genetics and Genomics (ACMG). In conclusion, this study described the phenotype and genotype of a patient with late-onset GA II. The two novel mutations in ETFDH were found in this case, which further expands the list of mutations found in patients with GA II. Because of the treatability of this disease, GA II should be considered in all patients with muscular symptoms and acute metabolism decompensation such as hypoglycemia and acidosis.
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spelling pubmed-99116582023-02-11 Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II Zhu, Sijia Ding, Dongxue Jiang, Jianhua Liu, Meirong Yu, Liqiang Fang, Qi Front Neurol Neurology Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Thus far, the high clinical heterogeneity of late-onset GA II has brought a great challenge for its diagnosis. In this study, we reported a 21-year-old Chinese man with muscle weakness, vomiting, and severe pain. Muscle biopsy revealed myopathological patterns of lipid storage myopathy, and urine organic acid analyses showed a slight increase in glycolic acid. All the aforementioned results were consistent with GA II. Whole-exome sequencing (WES), followed by bioinformatics and structural analyses, revealed two compound heterozygous missense mutations: c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11, which were classified as “likely pathogenic” according to American College of Medical Genetics and Genomics (ACMG). In conclusion, this study described the phenotype and genotype of a patient with late-onset GA II. The two novel mutations in ETFDH were found in this case, which further expands the list of mutations found in patients with GA II. Because of the treatability of this disease, GA II should be considered in all patients with muscular symptoms and acute metabolism decompensation such as hypoglycemia and acidosis. Frontiers Media S.A. 2023-01-27 /pmc/articles/PMC9911658/ /pubmed/36779069 http://dx.doi.org/10.3389/fneur.2023.1087421 Text en Copyright © 2023 Zhu, Ding, Jiang, Liu, Yu and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Zhu, Sijia
Ding, Dongxue
Jiang, Jianhua
Liu, Meirong
Yu, Liqiang
Fang, Qi
Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title_full Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title_fullStr Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title_full_unstemmed Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title_short Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II
title_sort case report: novel etfdh compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type ii
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911658/
https://www.ncbi.nlm.nih.gov/pubmed/36779069
http://dx.doi.org/10.3389/fneur.2023.1087421
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