Cargando…

Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China

PURPOSE: To characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients. METHODS: We analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China. RESULTS: 20 patients were diagnosed...

Descripción completa

Detalles Bibliográficos
Autores principales: E., Huishu, Liang, Lili, Zhang, Huiwen, Qiu, Wenjuan, Ye, Jun, Xu, Feng, Gong, Zhuwen, Gu, Xuefan, Han, Lianshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293753/
https://www.ncbi.nlm.nih.gov/pubmed/34306040
http://dx.doi.org/10.3389/fgene.2021.702374
_version_ 1783725109184299008
author E., Huishu
Liang, Lili
Zhang, Huiwen
Qiu, Wenjuan
Ye, Jun
Xu, Feng
Gong, Zhuwen
Gu, Xuefan
Han, Lianshu
author_facet E., Huishu
Liang, Lili
Zhang, Huiwen
Qiu, Wenjuan
Ye, Jun
Xu, Feng
Gong, Zhuwen
Gu, Xuefan
Han, Lianshu
author_sort E., Huishu
collection PubMed
description PURPOSE: To characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients. METHODS: We analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China. RESULTS: 20 patients were diagnosed by newborn screening and the remaining 81 cases were identified following clinical intervention. Macrocephaly was the most common presentation, followed by movement disorders and seizures. A total of 59 patients were evaluated by brain MRI and 58 patients presented with abnormalities, with widening of the sylvian fissures being the most common symptom. The concentration of glutarylcarnitine in the blood, glutarylcarnitine/capryloylcarnitine ratio, and urine levels of glutaric acid were increased in GA1 patients and were shown to decrease following intervention. A total of 88 patient samples were available for genotyping and 74 variants within the GCDH gene, including 23 novel variants, were identified. The most common variant was c.1244-2A > C (18.4%) and there were no significant differences in the biochemical or clinical phenotypes described for patients with the four most common variants: c.1244-2A > C, c.1064G > A, c.533G > A, and c.1147C > T. Patients identified by newborn screening had better outcomes than clinical patients. CONCLUSION: Our findings expand the spectrum of phenotypes and genotypes for GA1 in Chinese populations and suggest that an expanded newborn screening program using tandem mass spectrometry may facilitate the early diagnosis and treatment of this disease, improving clinical outcomes for patients in China.
format Online
Article
Text
id pubmed-8293753
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82937532021-07-22 Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China E., Huishu Liang, Lili Zhang, Huiwen Qiu, Wenjuan Ye, Jun Xu, Feng Gong, Zhuwen Gu, Xuefan Han, Lianshu Front Genet Genetics PURPOSE: To characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients. METHODS: We analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China. RESULTS: 20 patients were diagnosed by newborn screening and the remaining 81 cases were identified following clinical intervention. Macrocephaly was the most common presentation, followed by movement disorders and seizures. A total of 59 patients were evaluated by brain MRI and 58 patients presented with abnormalities, with widening of the sylvian fissures being the most common symptom. The concentration of glutarylcarnitine in the blood, glutarylcarnitine/capryloylcarnitine ratio, and urine levels of glutaric acid were increased in GA1 patients and were shown to decrease following intervention. A total of 88 patient samples were available for genotyping and 74 variants within the GCDH gene, including 23 novel variants, were identified. The most common variant was c.1244-2A > C (18.4%) and there were no significant differences in the biochemical or clinical phenotypes described for patients with the four most common variants: c.1244-2A > C, c.1064G > A, c.533G > A, and c.1147C > T. Patients identified by newborn screening had better outcomes than clinical patients. CONCLUSION: Our findings expand the spectrum of phenotypes and genotypes for GA1 in Chinese populations and suggest that an expanded newborn screening program using tandem mass spectrometry may facilitate the early diagnosis and treatment of this disease, improving clinical outcomes for patients in China. Frontiers Media S.A. 2021-07-07 /pmc/articles/PMC8293753/ /pubmed/34306040 http://dx.doi.org/10.3389/fgene.2021.702374 Text en Copyright © 2021 E, Liang, Zhang, Qiu, Ye, Xu, Gong, Gu and Han. 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 Genetics
E., Huishu
Liang, Lili
Zhang, Huiwen
Qiu, Wenjuan
Ye, Jun
Xu, Feng
Gong, Zhuwen
Gu, Xuefan
Han, Lianshu
Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title_full Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title_fullStr Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title_full_unstemmed Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title_short Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
title_sort evaluation of the clinical, biochemical, neurological, and genetic presentations of glutaric aciduria type 1 in patients from china
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293753/
https://www.ncbi.nlm.nih.gov/pubmed/34306040
http://dx.doi.org/10.3389/fgene.2021.702374
work_keys_str_mv AT ehuishu evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT lianglili evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT zhanghuiwen evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT qiuwenjuan evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT yejun evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT xufeng evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT gongzhuwen evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT guxuefan evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina
AT hanlianshu evaluationoftheclinicalbiochemicalneurologicalandgeneticpresentationsofglutaricaciduriatype1inpatientsfromchina