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

Qingqing Hu,Yan Liu,Tangfeng Su,Yuechi Shen,Sanqing Xu

doi:10.3389/fgene.2021.734481

Qingqing Hu, Yan Liu + Show 3 more

Open Access

PDF Available

https://doi.org/10.3389/fgene.2021.734481

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

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.

Highlights

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by impaired glucose transport through the blood–brain barrier and inherited in an autosomal dominant trait, which results from mutations of SLC2A1 gene encoding GLUT1 (Brockmann et al, 2001; Klepper et al, 2001)
The classic phenotype is characterized by refractory infantile epilepsy, developmental delay, acquired microcephaly, and complex movement disorders, such as ataxia, dystonia, and spasticity, which was first described by De Vivo et al in 1991 (De Vivo et al, 1991)
Epileptic seizures were reported in 25 patients (83.3%), presenting as the first symptom in 23 patients (76.7%) during infancy

Summary

Introduction

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by impaired glucose transport through the blood–brain barrier and inherited in an autosomal dominant trait, which results from mutations of SLC2A1 gene encoding GLUT1 (Brockmann et al, 2001; Klepper et al, 2001). The classic phenotype is characterized by refractory infantile epilepsy, developmental delay, acquired microcephaly, and complex movement disorders, such as ataxia, dystonia, and spasticity, which was first described by De Vivo et al in 1991 (De Vivo et al, 1991). Over the past few decades, its clinical spectrum has broadened to include non-classic phenotypes, such as paroxysmal exercise-induced dyskinesia and epilepsy, paroxysmal choreoathetosis with spasticity, atypical childhood absence epilepsy, and myoclonic astatic epilepsy (Wang et al, 2018). Paroxysmal non-epileptic events, including intermittent ataxia, paroxysmal eyeball movements, dysarthria, migraine, alternating hemiplegia, spastic paraparesis, and periodic confusion (De Giorgis and Veggiotti, 2013; Pearson et al, 2013; Nicita et al, 2019), and some extraneurologic features, like hemolytic anemia and cataracts, have been described (Weber et al, 2008; Flatt et al, 2011; Bawazir et al, 2012). Liang et al (2019) Liang et al (2019) Wei et al (2019) Zha et al (2019) Zha et al (2019) Pei et al (2020)

Results

Discussion

Conclusion