[Infant glycogen storage disease type Ⅳ: a clinicopathological and genetic characteristics analysis of five cases].

Objective: To investigate the clinical pathology and gene mutation characteristics of patients with glycogen storage disease type Ⅳ (GSD Ⅳ). Methods: The clinical data, liver histopathology and ultrastructural morphology, and gene sequencing results of 5 GSD Ⅳ cases diagnosed in the Children's Hospital Affiliated to Shanghai Jiaotong University School of Medicine and the Children's Hospital of Fudan University from January 2015 to February 2022 were collected and analyzed retrospectively. Results: Among the 5 cases, 3 were male and 2 were female, ranging in age from 4 months to 1 year and 9 months. The clinical manifestations included fever, hepatosplenomegaly, liver insufficiency, growth retardation and hypotonia. Four cases had liver biopsy showing ground-glass-like changes in hepatocytes with intracytoplasmic inclusion bodies and varying degrees of fibrosis. Liver electron microscopy in 2 cases showed that the level of glycogen increased to varying degrees, and the cytoplasm was filled with low electron density substances. Genetic testing revealed that 3 cases had compound heterozygous variants in GBE1 gene; 1 case had a single pathogenic variant in GBE1 gene; and 1 case was deceased with no genetic testing, but each parent was tested for a heterozygous variant in the GBE1 gene. A total of 9 GBE1 gene mutations were detected, 3 of which were reported mutations and 6 novel mutations. One case died of liver cirrhosis, and 1 case underwent autologous liver transplantation. After transplantation, the liver function basically returned to normal, and the growth and development improved; the other 3 cases were managed through diet control and symptomatic treatment. Conclusions: CSD Ⅳ is an extremely rare inherited metabolic disease caused by GBE1 gene mutation, often presenting with hepatic and neuromuscular disorders, with heterogeneous clinical manifestations. The diagnosis mainly depends on histopathology and a pedigree gene analysis.目的： 探讨糖原贮积病Ⅳ型（glycogen storage disease typeⅣ，GSD Ⅳ）的临床病理及基因突变特点。 方法： 收集上海交通大学医学院附属儿童医院及复旦大学附属儿科医院2015年1月至2022年2月确诊的5例GSD Ⅳ病例的临床资料、肝脏病理组织学、超微结构形态及基因测序结果，并对其进行回顾性分析。 结果： 5例病例中男患儿3例，女患儿2例，年龄为4个月至1岁9个月，主要表现为发热、肝脾肿大、肝功能不全、生长发育迟缓及肌力、肌张力低下。其中4例行肝脏活检，显示肝细胞毛玻璃样改变伴胞质内包涵体及不同程度纤维化。2例行肝脏电镜检查，显示糖原水平不同程度增多，胞质内充满低电子密度物质。基因检测发现其中3例GBE1基因存在复合杂合变异；1例检测到GBE1基因单个致病性变异；1例因死亡未能行基因检测，其父母各检测出GBE1基因有一个杂合变异。病例共检测到9种GBE1基因突变类型，3种为已报道的突变，6种为新的突变。1例因肝硬化死亡；1例行亲体肝移植，移植后肝功能基本恢复正常，生长发育情况得到改善；另外3例主要以饮食控制调整，支持对症治疗。 结论： GSD Ⅳ是由GBE1基因突变所致的一种极为罕见的遗传代谢性疾病，常累及肝脏及神经肌肉，临床表现有异质性，其诊断主要依据组织病理学及家系基因分析。.