22例肝糖原贮积症患者的临床特征和基因型分析

肝脏 ›› 2026, Vol. 31 ›› Issue (3): 412-419.

22例肝糖原贮积症患者的临床特征和基因型分析

单姗, 於海天, 檀玉乐, 申梨, 钟宇博, 周冬虎, 朱志军, 孙丽莹, 赵新颜

100050 北京首都医科大学附属北京友谊医院肝病中心,消化健康全国重点实验室,国家消化系统疾病临床医学研究中心(单姗,申梨,钟宇博,孙丽莹,赵新颜);
100069 北京首都医科大学附属北京佑安医院肝病中心一科(於海天);
100050 北京首都医科大学附属北京友谊医院肝移植中心,消化健康全国重点实验室,国家消化系统疾病临床医学研究中心,首都医科大学儿童肝脏移植临床诊疗与研究中心(檀玉乐,朱志军);
100050 北京北京市临床医学研究所,首都医科大学附属北京友谊医院(周冬虎)

收稿日期:2025-12-10 出版日期:2026-03-31 发布日期:2026-05-19
通讯作者: 赵新颜,Email:zhao_xinyan@ccmu.edu.cn
基金资助:
北京高层次创新创业人才支持计划领军人才(G202511024)

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

SHAN Shan¹, YU Hai-tian², TAN Yu-le³, SHEN Li¹, ZHONG Yu-bo¹, ZHOU Dong-hu⁴, ZHU Zhi-jun³, SUN Li-ying¹, ZHAO Xin-yan¹

1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing 100050, China;
2. The First Unit, Department of Hepatology, Beijing You′an Hospital, Capital Medical University, Beijing 100069, China;
3. Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 100050, China;
4. Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

Received:2025-12-10 Online:2026-03-31 Published:2026-05-19
Contact: ZHAO Xin-yan, Email: zhao_xinyan@ccmu.edu.cn

摘要/Abstract

摘要： 目的探讨肝糖原贮积症(GSD)患者的临床特征、肝脏病理表现、突变基因型分布、治疗及预后,以提高对这一罕见疾病的认识,并为临床精准诊疗提供依据。方法回顾性分析2014年1月至2025年12月于首都医科大学附属北京友谊医院确诊的肝GSD患者的临床资料,对其临床表现、生化指标、并发症及肝脏病理特征进行归纳分析,并比较不同亚型患者的临床特点。结果共纳入22例肝GSD患者,男、女各11例,包括儿童18例、成人4例,确诊中位年龄为6(3,16)岁。分型为GSDⅠa型7例、Ⅰb型4例、Ⅲ型4例、Ⅳ型4例及Ⅸ型3例。最常见的临床表现为肝大(81.82%)和肝功能异常(77.27%),确诊时13.64%患者处于肝硬化代偿期,18.18%已进展至失代偿期。肝组织学表现为肝细胞肿胀、糖原核易见,Ⅰ型患者常伴有轻、中度肝细胞脂肪变性,Ⅲ、Ⅳ、Ⅸ型患者的肝纤维化程度较重。本研究共检出28个GSD相关基因变异,包含11个新变异,热点变异为G6PC1 c.648G>T。所有患者均接受以生玉米淀粉为基础的对症治疗,11例患者接受了肝移植。结论不同类型的肝GSD临床表现重叠,Ⅲ型及Ⅳ型更易进展为肝硬化,存在诊断延迟现象。基因检测是确诊和分型的重要方法,有助于预后评估。以生玉米淀粉为基础的综合管理是主要治疗手段,肝移植适用于终末期患者,基因治疗是未来有前景的方向。

关键词: 糖原贮积症, 基因型, 临床表现, 病理特征, 肝硬化

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

单姗, 於海天, 檀玉乐, 申梨, 钟宇博, 周冬虎, 朱志军, 孙丽莹, 赵新颜. 22例肝糖原贮积症患者的临床特征和基因型分析[J]. 肝脏, 2026, 31(3): 412-419.

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.

/ 推荐

参考文献

[1] Hannah W B, Derks T G J, Drumm M L, et al. Glycogen storage diseases[J]. Nat Rev Dis Primers, 2023, 9(1): 46.
[2] Wright T L F, Umaña L A, Ramirez C M. Update on glycogen storage disease: primary hepatic involvement[J]. Curr Opin Pediatr, 2022, 34(5): 496-502.
[3] 中华医学会儿科学分会儿童保健学组, 中华医学会儿科学分会心血管学组. 儿童青少年血脂异常防治专家共识[J]. 中华儿科杂志, 2009, 47(6): 426-428.
[4] 中国血脂管理指南修订联合专家委员会, 王增武, 李建军, 等. 中国血脂管理指南(基层版2024年)[J]. 中国全科医学 2024, 27(20): 2429-2436.
[5] 中国民族卫生协会重症代谢疾病分会, 高尿酸血症相关疾病诊疗多学科共识专家组. 中国高尿酸血症相关疾病诊疗多学科专家共识(2023年版)[J]. 中国实用内科杂志, 2023, 43(6): 461-480.
[6] 中华医学会血液学分会红细胞疾病(贫血)学组. 中性粒细胞减少症诊治中国专家共识[J]. 中华医学杂志, 2022, 102(40): 3167-3173.
[7] Kishnani P S, Goldstein J, Austin S L, et al. Diagnosis and management of glycogen storage diseases type Ⅵ and Ⅸ: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2019, 21(4): 772-789.
[8] Liang Y, Du C, Wei H, et al. Genotypic and clinical analysis of 49 Chinese children with hepatic glycogen storage diseases[J]. Mol Genet Genomic Med, 2020, 8(10): e1444.
[9] Kor D, Bulut F D, Köşeci B, et al. Clinical features and rare complications in 132 patients with hepatic glycogenosis[J]. Orphanet J Rare Dis, 2025, 20(1): 398.
[10] Kumar T V, Bhat M, Narayanachar S G, et al. Molecular and clinical profiling in a large cohort of Asian Indians with glycogen storage disorders[J]. PloS One, 2022, 17(7): e0270373.
[11] 张雪媛, 张萍, 冯佳燕. 等.糖原贮积病Ⅲ型26例患儿的基因及其临床特征[J]. 中华肝脏病杂志, 2024, 32(11): 1005-1012.
[12] Magoulas P L, El-Hattab A W, Roy A, et al. Diffuse reticuloendothelial system involvement in type Ⅳ glycogen storage disease with a novel GBE1 mutation: a case report and review[J]. Hum Pathol, 2012, 43(6):943-951.
[13] Kishnani P S, Austin S L, Abdenur J E, et al. Diagnosis and management of glycogen storage disease type Ⅰ: a practice guideline of the American College of Medical Genetics and Genomics[J]. Genet Med, 2014, 16(11): e1.
[14] 帅佳瑜. 72例儿童肝糖原累积症临床分析及随访[D].重庆医科大学, 2019.
[15] 孙爽. 84例糖原累积症的临床特点总结及文献复习[D].广西医科大学, 2022.
[16] Al-Hussaini A, AlMannai M, Alruwaithi M, et al. Clinical and molecular characterization of hepatic glycogen storage disease in Saudi Arabia[J]. PloS One, 2025, 20(7): e0329008.
[17] 赵素贤, 刘世恒, 李文聪, 等. 10例儿童肝糖原累积病临床及病理学分析[J]. 临床肝胆病杂志, 2022, 38(8): 1839-1842.
[18] Luo X, Duan Y, Fang D, et al. Diagnosis and follow-up of glycogen storage disease (GSD) type Ⅵ from the largest GSD center in China[J]. Hum Mutat, 2022, 43(5): 557-567.
[19] Sun C, Du T, Xia Y, et al. Clinical and genetic analyses of 17 Chinese patients with glycogen storage disease type Ⅸc[J]. Orphanet J Rare Dis, 2025.
[20 ] Xu Y, Liu Y, Yuan Y, et al. Clinical characteristics of 50 hepatocellular adenoma patients among 164 cases of glycogen storage disease type Ⅰa[J]. Eur J Pediatr, 2025, 184(7): 458.
[21] Shimizu S, Sakamoto S, Yamada M, et al. Immunological features and complications in patients with glycogen storage disease Ⅰb after living donor liver transplantation[J]. Pediatr Transplant, 2021, 25(8): e14104.
[22] Wang H, Qu W, Liu Y, et al. Recurrence of myopathy after liver transplantation for patients with end-stage GSD type Ⅲa[J]. Transplant Proc, 2025, 57(3): 475-480.
[23] Weinstein D A, Derks T G, Rodriguez-Buritica D F, et al. Safety and efficacy of DTX401, an AAV8-mediated liver-directed gene therapy, in adults with glycogen storage disease type Ⅰa (GSDIa)[J].J Inherit Metab Dis, 2025, 48(2): e70014.