Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review

Objective: GLUT1 deficiency syndrome (GLUT1-DS) is a rare, treatable neurometabolic disorder. However, its diagnosis may be challenging due to the various and evolving phenotypes. Here we report the first Chinese familial cases with genetically confirmed GLUT1-DS and analyze the characteristics of C...

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Autores principales:	Qingqing Hu, Yuechi Shen, Tangfeng Su, Yan Liu, Sanqing Xu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	GLUT1 deficiency syndrome epilepsy developmental delay movement disorders SLC2A1 gene Genetics QH426-470
Acceso en línea:	https://doaj.org/article/a76b2d250d0c40769e97dd5da5a4a8d2
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spelling	oai:doaj.org-article:a76b2d250d0c40769e97dd5da5a4a8d22021-11-22T06:58:51ZClinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review1664-802110.3389/fgene.2021.734481https://doaj.org/article/a76b2d250d0c40769e97dd5da5a4a8d22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.734481/fullhttps://doaj.org/toc/1664-8021Objective: GLUT1 deficiency syndrome (GLUT1-DS) is a rare, treatable neurometabolic disorder. However, its diagnosis may be challenging due to the various and evolving phenotypes. Here we report the first Chinese familial cases with genetically confirmed GLUT1-DS and analyze the characteristics of Chinese children with GLUT1-DS from clinical, laboratory, and genetic aspects.Methods: We reported a Chinese family with three members affected with GLUT1-DS and searched for relevant articles up to September 2020 from PubMed, WOS, CNKI, and WanFang databases. A total of 30 Chinese patients diagnosed with GLUT1-DS (three newly identified patients in one family and 27 previously reported ones) were included and analyzed in this study.Results: The median age of onset of the 30 patients (male: 18, female: 12) was 8.5 months (range, 33 days to 10 years). Epileptic seizures were found in 25 patients, most with generalized tonic–clonic and focal ones. Movement disorders were found in 20 patients—frequently with ataxia and dystonia, developmental delay in 25 patients, and microcephaly only in six patients. The cerebrospinal fluid (CSF) analysis showed decreased CSF glucose (median: 1.63 mmol/L, range: 1.1–2.6 mmol/L) and glucose ratio of CSF to blood (median: 0.340; range: 0.215–0.484). The genetic testing performed in 28 patients revealed 27 cases with pathogenic variations of the SLC2A1 gene, including 10 missense, nine frameshift, three nonsense, three large fragment deletions, and two splice-site mutations. Most patients had a good response to the treatment of ketogenic diet or regular diet with increased frequency. Although three patients in this Chinese family carried the same pathogenic mutation c.73C > T (p.Q25X) in the SLC2A1 gene, their symptoms and responses to treatment were not exactly the same.Conclusion: The clinical manifestations of GLUT1-DS are heterogeneous, even among family members sharing the same mutation. For children with unexplained epileptic seizures, developmental delay, and complex movement disorders, detection of low CSF glucose or SLC2A1 gene mutations is helpful for the diagnosis of GLUT1-DS. Early initiation of ketogenic diet treatment significantly improves the symptoms and prognosis of GLUT1-DS.Qingqing HuQingqing HuYuechi ShenTangfeng SuYan LiuSanqing XuFrontiers Media S.A.articleGLUT1 deficiency syndromeepilepsydevelopmental delaymovement disordersSLC2A1 geneGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GLUT1 deficiency syndrome epilepsy developmental delay movement disorders SLC2A1 gene Genetics QH426-470
spellingShingle	GLUT1 deficiency syndrome epilepsy developmental delay movement disorders SLC2A1 gene Genetics QH426-470 Qingqing Hu Qingqing Hu Yuechi Shen Tangfeng Su Yan Liu Sanqing Xu Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
description	Objective: GLUT1 deficiency syndrome (GLUT1-DS) is a rare, treatable neurometabolic disorder. However, its diagnosis may be challenging due to the various and evolving phenotypes. Here we report the first Chinese familial cases with genetically confirmed GLUT1-DS and analyze the characteristics of Chinese children with GLUT1-DS from clinical, laboratory, and genetic aspects.Methods: We reported a Chinese family with three members affected with GLUT1-DS and searched for relevant articles up to September 2020 from PubMed, WOS, CNKI, and WanFang databases. A total of 30 Chinese patients diagnosed with GLUT1-DS (three newly identified patients in one family and 27 previously reported ones) were included and analyzed in this study.Results: The median age of onset of the 30 patients (male: 18, female: 12) was 8.5 months (range, 33 days to 10 years). Epileptic seizures were found in 25 patients, most with generalized tonic–clonic and focal ones. Movement disorders were found in 20 patients—frequently with ataxia and dystonia, developmental delay in 25 patients, and microcephaly only in six patients. The cerebrospinal fluid (CSF) analysis showed decreased CSF glucose (median: 1.63 mmol/L, range: 1.1–2.6 mmol/L) and glucose ratio of CSF to blood (median: 0.340; range: 0.215–0.484). The genetic testing performed in 28 patients revealed 27 cases with pathogenic variations of the SLC2A1 gene, including 10 missense, nine frameshift, three nonsense, three large fragment deletions, and two splice-site mutations. Most patients had a good response to the treatment of ketogenic diet or regular diet with increased frequency. Although three patients in this Chinese family carried the same pathogenic mutation c.73C > T (p.Q25X) in the SLC2A1 gene, their symptoms and responses to treatment were not exactly the same.Conclusion: The clinical manifestations of GLUT1-DS are heterogeneous, even among family members sharing the same mutation. For children with unexplained epileptic seizures, developmental delay, and complex movement disorders, detection of low CSF glucose or SLC2A1 gene mutations is helpful for the diagnosis of GLUT1-DS. Early initiation of ketogenic diet treatment significantly improves the symptoms and prognosis of GLUT1-DS.
format	article
author	Qingqing Hu Qingqing Hu Yuechi Shen Tangfeng Su Yan Liu Sanqing Xu
author_facet	Qingqing Hu Qingqing Hu Yuechi Shen Tangfeng Su Yan Liu Sanqing Xu
author_sort	Qingqing Hu
title	Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
title_short	Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
title_full	Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
title_fullStr	Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
title_full_unstemmed	Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review
title_sort	clinical and genetic characteristics of chinese children with glut1 deficiency syndrome: case report and literature review
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a76b2d250d0c40769e97dd5da5a4a8d2
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Clinical and Genetic Characteristics of Chinese Children With GLUT1 Deficiency Syndrome: Case Report and Literature Review

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