Introduction: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) andglucose-6-phosphate transporter (SLC37A4), respectively[1, 2]. GSD 1 is characterized by chubby face, hypoglycemia, hyperlipidemia, hyperuricemia, hepatomegaly, nephromegaly and growth retardation. GSD1b patients also show neutropenia and/or neutrophil dysfunction[3, 4]. This study designates to evaluate the clinical and genetic characteristics of patients with clinical symptoms suggestive
GSD1 to assess the possible genotype-phenotype correlation Materials & Methods: 10 Iranian patients from nine unrelated families with GSD I wereincluded. Direct sequencing of the coding region and splicing-sites in the G6PC and SLC37A4 genes were performed to mutation screening.Results: Mutation analysis revealed four causative variants. The known mutation c.247C> T (p.R83C) in G6PC. The recurrent mutation of c.1042_1043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G> A (p.G122E) in the homozygous state were identified in theSLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. Furthermore, a novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Consanguinity was detected in all cases. Almost all GSD1a patients with Known mutation presented the common clinical and laboratory findings. However, there were significant differences in the clinical and biochemical parameters indicating heterogeneity between GSD1b patients. Severe and moderate neutropenia was observed in patients with frameshift and missense variants of SLC37A4, respectively. The sibling with the SLC37A4 gene deletion has shown both severe neutropenia and leukopeniaConclusion & discussion: The results showed: 1) two novel mutations revealed in SLC37A4, and 2) the hematological findings in GSD1b patients may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed.