糖原贮积病Ⅲ型26例患儿的基因及其临床特征

Genetic and clinical characteristics of 26 cases with glycogen storage disease typeⅢ

目的探讨糖原贮积病Ⅲ型(GSDⅢ)患者基因、临床特点及治疗后的特征。方法采用回顾性队列研究。收集2017年6月—2023年12月在复旦大学附属儿科医院就诊的26例GSDⅢ型患儿的基因和临床资料。依据AGL基因变异类型分为非错义变异组和错义变异组,分析基因型与表型的相关性。所有患者诊断后予生玉米淀粉治疗,对随访超过12个月的患者比较治疗前后的变化。以P<0.05表示差异具有统计学意义。结果纳入的26例患者中男13例、女13例,确诊的中位年龄为28(6,134)个月。共检出35种AGL基因变异,热点变异为c.1735+1G>T(9/52,17.3%)。常见临床表现为转氨酶升高(26/26,100%)、肝肿大(25/26,96.2%)、空腹低血糖(25/26,96.2%)及高血酮(16/18,88.9%)、高甘油三酯(TG)(20/26,76.9%)、高肌酸激酶(CK)(16/25,64.0%)、心电图异常(12/16,75.0%)。诊断时有肌病症状的患者15.4%(4例)。18例进行肝脏穿刺术,其中肝纤维化≥S283.3%(15/18)。非错义变异组与错义变异组相比,高CK、高丙氨酸转氨酶(ALT)病例数较多(P值均<0.05)。余在年龄、身高、肝脏大小及纤维化程度、空腹血糖(Glu)、TG差异无统计学意义(P值均>0.05)。14例患者中位随访时间为40.5(20,73)个月,身高改善,肝脏缩小,ALT、TG降低,Glu改善,但28.6%(4例)新发肌病症状,CK升高(P值均<0.05)。随年龄的增长ALT下降,CK水平增加(P值均<0.05)。结论我国GSDⅢ型诊断时常见的临床表现为转氨酶升高、肝肿大、空腹低血糖及高血酮、高甘油三酯血症、CK升高,早期可出现肝纤维化。生玉米淀粉治疗后身高、肝脏及代谢相关指标可改善,但肌病可进展。

ObjectiveTo investigate the genetic,clinical,and post-treatment characteristics of patients with glycogen storage disease typeⅢ(GSDⅢ).MethodsA retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSDⅢwho visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023.The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed.All patients were treated with uncooked cornstarch after diagnosis.The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up.A P value of<0.05 was used to denote statistical significance.ResultsAmong the 26 cases enrolled,13 were female and 13 were male,and the median age of diagnosis was 28(6 to 134)months.A total of thirty-five different types of AGL gene variation were detected,with c.1735+1G>T(9/52,17.3%)as the hotspot variation.The common clinical manifestations were elevated aminotransferases(26/26,100%),hepatomegaly(25/26,96.2%),fasting hypoglycemia(25/26,96.2%),hyperketonemia(16/18,88.9%),hypertriglyceridemia(TG)(20/26,76.9%),elevated CK(16/25,64.0%),and an abnormal electrocardiogram(12/16,75.0%).Four cases(15.4%)had symptoms of myopathy at diagnosis.Liver biopsy was performed in eighteen cases,among whom 83.3%(15/18)had liver fibrosis≥S2.The number of cases with elevated levels of CK(P=0.031)and ALT(P=0.038)was pronounced in the non-missense variation group compared to that in the missense variation group.There were no statistically significant differences in age,height,liver size,degree of fibrosis,fasting blood glucose(Glu)and TG(P>0.05).The median follow-up time of 14 cases was 40.5(20-73)months,with improvement in body stature,reduced liver size,decreased ALT and TG,and improved Glu.However,four(28.6%)cases had new myopathy symptoms with raised CK(P<0.05)and with advancing age,increased ALT diminished while CK level elevated(P<0.05).ConclusionsThe common clinical manifestations at the early stage of the GSDⅢdiagnosis are elevated aminotransferases,hepatomegaly,fasting hypoglycemia,hyperketonemia,high triglycerides,elevated CK,and fibrotic liver in China.Myopathy symptoms may arise following uncooked cornstarch treatment;however,there is significant improvement in height,liver-related,and metabolic parameters.