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 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.

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GLUT1 deficiency syndrome: A case report with a novel SLC2A1 mutation

Vojnosanitetski pregled ◽

10.2298/vsp170406120i ◽

2019 ◽

Vol 76 (5) ◽

pp. 543-546 ◽

Cited By ~ 1

Author(s):

Nikola Ivancevic ◽

Natasa Cerovac ◽

Blazo Nikolic ◽

Goran Cuturilo ◽

Ana Marjanovic ◽

...

Keyword(s):

Case Report ◽

Developmental Delay ◽

Ketogenic Diet ◽

Glucose Transporter ◽

Deficiency Syndrome ◽

Chromosome 1 ◽

Brain Membrane ◽

Slc2a1 Gene ◽

Glut1 Deficiency ◽

Glut1 Deficiency Syndrome

Introduction. GLUT1 deficiency syndrome (GLUT1 DS, OMIM 606777) is a metabolic brain disorder caused by mutations in SLC2A1 gene (chromosome 1) encoding glucose transporter type 1 located on blood-brain membrane. The ?classic? phenotype in children includes early onset generalized farmacoresistant epilepsy, developmental delay, complex movement disorders and acquired microcephaly. However, there are milder phenotypes without epilepsy which could be seen in older children. The ketogenic diet is a treatment of choice. Case report. We present a four-yearold female patient with farmacoresistant generalized epilepsy, paroxysmal dystonic posturing, ataxia, hypotonia, developmental delay (motor, attention and speech disturbances), and microcephaly. The genetic testing revealed a novel point mutation at c.156T > A (p.Y52X) in exon 3 of SLC2A1 gene. The patient responded excellent on ketogenic diet. Conclusion. GLUT1 DS is treatable, and likely to be under-diagnosed neurological disorder. The ketogenic diet is resulting in good control of seizures in the patients, and it has certain benefit for the neurodevelopmental disability.

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