Frequency of G6PC1 and SLC37A4 Genetic Variants in Asian Patients With Glycogen Storage Disease Type I: A Systematic Review

Abstract

Background: Glycogen storage disease type I (GSD I), or Von Gierke disease, is a rare autosomal recessive disorder caused by mutations in the G6PC1 (GSD Ia) or SLC37A4 (GSD Ib) genes. Early genetic diagnosis is essential to prevent complications. Objectives: This study aimed to systematically review reported G6PC1 and SLC37A4 variants in Asian patients and to identify region-specific mutation patterns. Methods: A systematic search of Web of Science, PubMed, Embase, Scopus, ProQuest, and Google Scholar was performed through June 4, 2023, using appropriate MeSH terms and keywords. Eligible studies included cross-sectional studies, cohorts, case reports/series, and case-control designs that reported the type and frequency of pathogenic or likely pathogenic G6PC1 or SLC37A4 variants in Asian patients with GSD I. Two reviewers independently extracted data, with discrepancies resolved by a third reviewer. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics (ACMG) criteria and cross-validated with ClinVar and HGMD. Regional variant frequencies were summarized using descriptive methods. Results: Seventy studies from 14 Asian countries, comprising 680 patients, were included. Distinct regional mutation patterns were identified. In East Asia, the G6PC1 c.648G>T and SLC37A4 c.572C>T/c.521C>T variants predominated. In West Asia, G6PC1 c.247C>T and SLC37A4 c.10421043delCT were most frequent. In South Asia, G6PC1 c.648G>T/c.150151delGT and SLC37A4 c.796797del/c.898C>T were common. These patterns highlight both shared and region-specific variants. Conclusions: The study reveals diverse, region-specific G6PC1 and SLC37A4 mutations in Asian patients with GSD I, supporting targeted genetic screening and personalized diagnostics.