Genotype-phenotype spectrum and clinical outcomes of glycogen storage disease type I: A 15-year experience at Vietnam National Children's Hospital.

BACKGROUND

Glycogen Storage Disease Type I (GSD I) is an inherited metabolic disorder characterized by impaired hepatic glucose production due to defects in gluconeogenesis and glycogenolysis. Two subtypes are recognized: GSD Ia (G6PC) and GSD Ib (SLC37A4). Genotype-phenotype correlations and long-term outcomes in Southeast Asia remain insufficiently characterized. This study aimed to describe the clinical, biochemical, and molecular features of Vietnamese children with GSD I and evaluate treatment outcomes .

METHODS

Twenty-four patients from 19 families diagnosed at the Vietnam National Children's Hospital between 2016 and 2025 were included. All underwent genetic testing. Clinical characteristics and laboratory parameters were collected at diagnosis and during follow-up .

RESULTS

Twelve distinct variants were identified, including eight in G6PC and four in SLC37A4, with one novel variant (c.1193G > A). The most common G6PC variants were c.518 T > C, c.356 A > T, and c.648G > T, while c.706_708delGTG predominated in SLC37A4. The median age at symptom onset was 4 months, and 70% of patients presented with hepatomegaly. Elevated liver enzymes and lactate levels were observed in all cases, and 88.2% had hypertriglyceridemia. Dietary adherence was generally poor despite uncooked cornstarch therapy. During follow-up, patients with GSD Ia developed complications including short stature, hepatic adenoma, pancreatitis, hypertension, kidney stones, and cirrhosis, while all GSD Ib patients experienced neutropenia and required empagliflozin for recurrent infections .

CONCLUSION

Hepatomegaly with elevated liver enzymes, lactate, and triglycerides is a common presentation of GSD I. Variant distribution may differ across populations, and complications can occur at any age.