Hepatic glycogen storage disease: Deciphering the genotype-phenotype conundrum

Abstract

Glycogen storage diseases (GSDs) are a group of inherited disorders caused by genetic defects in various enzymes involved in glycogen production or breakdown. Hepatic GSDs often have overlapping clinical features, making subtyping or prognostication difficult. With the availability and advancement of next-generation sequencing, definitive molecular diagnosis is now available for most patients, with newer variants being increasingly identified. Molecular diagnosis could help in systematic follow-up, anticipating complications and prognostications. However, the mutations reported in the published literature display wide variations across racial and geographical groups. Hence, natural history, long-term outcome, and genotype-phenotypic correlation studies in patients with various hepatic GSDs are needed for a deeper understanding. Considering the emerging evidence of genetic profiling of patients with hepatic GSDs, including the recent study by Vanduangden et al, this editorial aims to review the various clinical subtypes, the spectrum of genetic mutations, and genotype-phenotype correlations for various hepatic GSDs.

Keywords: Children; Genotype-phenotype correlation; Hepatic glycogen storage disease; Metabolic control; Next-generation sequencing.