Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand.

Background: Thus far, genetic analysis of patients clinically diagnosed with glycogen storage diseases (GSDs) in Thailand has not been reported.

Aim: To evaluate the clinical and biochemical profiles, molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD.

Methods: Children aged < 18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited. Whole-exome sequencing (WES) was performed to identify the causative gene variants. Medical records were assessed.

Results: All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia ( = 1), III ( = 3), VI ( = 3), and IX ( = 1). A total number of 10 variants were identified including ( = 1), ( = 4), ( = 5), and ( = 1). had two novel variants. The clinical manifestations were hepatomegaly ( = 8), doll-like facies ( = 3), wasting ( = 2), and stunting ( = 5). All patients showed hypoglycemia, transaminitis, and dyslipidemia. The mainstay of treatment was cornstarch supplementation and high-protein and low-lactose-fructose diet. After a median follow-up time of 9.59 years, height turned to normal for age in 3/5 patients and none had malnutrition. Liver enzymes, blood sugar, and lipid profiles improved in all.

Conclusion: Hepatomegaly, transaminitis, and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology. Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment, prognosis, and long-term care.