Analysis of clinical characteristics and genotypes in 22 cases of glycogen storage disease

Abstract

Abstract: Objective To explore the clinical and hepatic pathological features, mutation genotype distribution, treatment, and prognosis of patients with hepatic glycogen storage disease (GSD), and to deepen understanding of this rare disease and provide a basis for precise clinical management. Methods A retrospective cohort study was conducted, collecting clinical data from patients with hepatic GSD treated at Beijing Friendship Hospital, Capital Medical University, between January 2014 and December 2025. Clinical manifestations, biochemical abnormalities, complications, and hepatic pathological features were summarized. Clinical characteristics were compared among different subtypes of hepatic GSD. Results A total of 22 patients with hepatic GSD were included, comprising 11 males and 11 females. Among them, 18 were children and 4 were adults, with a median age at diagnosis of 6 (3, 16) years. Subtype distribution included GSD Ⅰa (7 cases), GSD Ⅰb (4 cases), GSD Ⅲ (4 cases), GSD Ⅳ (4 cases), and GSD Ⅸ (3 cases). The most common clinical manifestations were hepatomegaly (81.82%) and abnormal liver function (77.27%). 13.64% of patients were in the compensated stage of cirrhosis, while 18.18% had progressed to decompensated cirrhosis at diagnosis. Histological findings included hepatocyte swelling and frequent glycogen nuclei. Patients with type Ⅰ GSD often exhibited mild to moderate hepatocyte steatosis, whereas those with types Ⅲ, Ⅳ, and Ⅸ showed more severe hepatic fibrosis. A total of 28 GSD-related gene variants were identified, including 11 novel variants, with G6PC1 c.648G>T being a hotspot mutation. All patients received symptomatic treatment based on uncooked cornstarch, and 11 underwent liver transplantation. Conclusion Different types of hepatic GSD exhibited overlapping clinical manifestations, and type Ⅲ and Ⅳ are more prone to progress to cirrhosis, indicating possible diagnostic delay. Genetic testing is essential for definitive diagnosis and subtyping and may aid in prognostic evaluation. Comprehensive management centered on uncooked cornstarch remains the mainstay of treatment. Liver transplantation is reserved for endstage cases. Gene therapy represents a promising future direction.

Key words: Glycogen storage disease, Genotype, Clinical phenotype, Pathological feature, Liver cirrhosis

SHAN Shan, YU Hai-tian, TAN Yu-le, SHEN Li, ZHONG Yu-bo, ZHOU Dong-hu, ZHU Zhi-jun, SUN Li-ying, ZHAO Xin-yan. Analysis of clinical characteristics and genotypes in 22 cases of glycogen storage disease[J]. Chinese Hepatolgy, 2026, 31(3): 412-419.

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