Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia

Wen-Hao Yu; Li-Wen Chen; Shan-Tair Wang; Yi-Fang Tu; Chao-Ching Huang

doi:10.1016/j.braindev.2019.07.004

Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia

Brain Dev. 2019 Nov;41(10):854-861. doi: 10.1016/j.braindev.2019.07.004. Epub 2019 Jul 17.

Authors

Wen-Hao Yu¹, Li-Wen Chen¹, Shan-Tair Wang², Yi-Fang Tu¹, Chao-Ching Huang³

Affiliations

¹ Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Graduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Gerontology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: huangped@tmu.edu.tw.

PMID: 31326153
DOI: 10.1016/j.braindev.2019.07.004

Abstract

Introduction: The neurodevelopmental outcomes of young infants with hypoglycorrhachia that is comparable to glucose transporter 1 deficiency syndrome (GLUT1DS), i.e. cerebrospinal fluid (CSF) glucose ≤40 mg/dL and CSF lactate <2.2 mM without causes of secondary hypoglycorrhachia are unknown. This study investigated the developmental outcomes and possibility of GLUT1DS in infants with hypoglycorrhachia, or low CSF glucose concentration.

Material and methods: 1655 neurologically asymptomatic infants aged <4 months had CSF examinations for fever workup from 2006 to 2016. Among the infants with normal CSF cell counts and without isolated pathogens, there were hypoglycorrhachia group who had CSF glucose levels that were comparable to GLUT1DS, and age- and gender-matched non-hypoglycorrhachia group. Both groups were at a mean age of 5.9 ± 2.4 years (ranged 1-10 years) at neurodevelopmental evaluation in 2017. Mutational analysis of solute-carrier-family 2, which facilitated the glucose transporter member 1 (SLC2A1) gene was performed.

Results: Among the 722 infants with normal CSF cell counts and without isolated pathogens, 30 (4.2%) had hypoglycorrhachia that was comparable to GLUT1DS. In the 25 infants with hypoglycorrhachia available for follow-up, 4 (16%) had abnormal outcomes, of which 3 (12%) had the history of mixed-type developmental delay before age 6 and 1 (4%) had type 1 diabetes mellitus. In the non-hypoglycorrhachia control group (n = 50), 2 patients (4%) showed abnormal outcomes, both with the history of pure speech delay. The hypoglycorrhachia group had a higher rate of the history of mixed-type of developmental delay than the control group (12% vs. 0%, P = 0.034). No SLC2A1 pathogenic variants were observed in the hypoglycorrhachia group.

Conclusion: Hypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.

Keywords: Glucose transporter 1 deficiency syndrome; Hypoglycorrhachia; Infant; SLC2A1.

MeSH terms

Carbohydrate Metabolism, Inborn Errors / genetics
Carbohydrate Metabolism, Inborn Errors / physiopathology
Case-Control Studies
Child, Preschool
DNA Mutational Analysis
Female
Glucose / cerebrospinal fluid*
Glucose / metabolism
Glucose Transporter Type 1 / genetics*
Glucose Transporter Type 1 / metabolism*
Humans
Infant
Infant, Newborn
Infant, Newborn, Diseases
Male
Monosaccharide Transport Proteins / deficiency
Monosaccharide Transport Proteins / genetics
Neurodevelopmental Disorders / etiology
Prevalence

Substances

Glucose Transporter Type 1
Monosaccharide Transport Proteins
SLC2A1 protein, human
Glucose

Supplementary concepts

Glut1 Deficiency Syndrome