以肝纤维化为早期表现的糖原贮积症IXa型1例

A Case Report of Glycogen Storage Disease Type IXa with Early Manifestation of Hepatic Fibrosis

摘要: 目的：总结1例经基因诊断的以肝纤维化为早期表现的糖原贮积症(Glycogen Storage Disease, GSD) IXa型患儿的临床特点、分子遗传学特征及生玉米淀粉治疗效果，为深化对该病临床和分子遗传学特征的认识积累资料。方法：回顾性分析1例4岁3月男童患者进行临床资料，采用二代测序技术对其一家三口标本进行基因诊断，分析基因变异及治疗数据。结果：患儿发病年龄1岁10月，临床表现为转氨酶升高、肝脏肿大伴肝纤维化、生长发育迟缓、高尿酸血症及高甘油三酯血症，基因分析发现患儿PHKA2基因存在c.1453A > T母源性半合子变异，该变异为未报道过的新变异，根据医学遗传学与基因组学学会指南(ACMG)评级为“致病性变异”，最终确诊糖原贮积症年龄为4岁3月。经3月的生玉米淀粉的早期治疗后，患儿肝脏弹性值恢复正常，转氨酶下降50%，但后续未规律随访。结论：PHKA2基因c.1453A > T半合子变异为新发现的致病性变异，拓展了该病的基因谱。该患儿以肝纤维化为早期表现，说明GSDIXa型并非绝对良性疾病。

Abstract: Objective: To summarize the clinical features, molecular genetic characteristics, and therapeutic efficacy of uncooked cornstarch in a genetically diagnosed boy with glycogen storage disease (GSD) type IXa presenting with early hepatic fibrosis, so as to accumulate evidence for further understanding of the clinical and molecular genetic profiles of this disorder. Methods: Clinical data of a 4-year-and-3-month-old male patient were retrospectively analyzed. Next-generation sequencing (NGS) was performed on peripheral blood samples from the patient and his parents for genetic diagnosis, followed by analysis of gene variants and therapeutic outcomes. Results: The patient first developed symptoms at 1 year and 10 months of age, characterized by elevated transaminases, hepatomegaly accompanied by hepatic fibrosis, growth retardation, hyperuricemia, and hypertriglyceridemia. Genetic testing identified a maternally inherited hemizygous variant c.1453A > T in the PHKA2 gene, a previously unreported novel variant classified as pathogenic according to the ACMG guidelines. The definitive diagnosis of GSD IXa was established at the age of 4 years and 3 months. After 3 months of early intervention with uncooked cornstarch, the patient’s liver stiffness measurement (LSM) returned to normal, and transaminase levels decreased by 50%. However, regular clinical follow-up was not maintained thereafter. Conclusion: The hemizygous PHKA2 c.1453A > T variant is a newly identified pathogenic variant that expands the mutational spectrum of GSD IXa. The presentation of early hepatic fibrosis in this patient indicates that GSD IXa is not an absolutely benign disorder.