PGK1基因变异致磷酸甘油酸激酶1缺乏症1例临床与遗传学分析

Clinical and genetic analysis of a child with phosphoglycerate kinase 1 deficiency by PGK1 gene mutation

目的探讨PGK 1基因变异致Ⅸ型糖原累积病(磷酸甘油酸激酶1缺乏症)的临床特点及诊疗方法。方法回顾分析1例磷酸甘油酸激酶1缺乏患儿临床资料,分析其临床特点及实验室检查结果,采用二代测序分析基因变异筛查结果。结果患儿男性,3岁11个月首次就诊。患儿每次均以抽搐起病,起病后病情迅速加重,出现反复抽搐发作,每次病程中均有溶血性贫血,第三次住院期间出现严重的横纹肌溶解症,且发病后有明显的智力、运动发育落后,基因检测显示患儿PGK 1基因错义变异(c.150C>G),该变异导致第50号氨基酸由Cys变为Trp,来自于母亲,其母为杂合子,符合X连锁隐性遗传方式,既往文献及数据库未见报道。根据ACMG指南,此变异判定为可能致病性(基因检测时,尚未出现横纹肌溶解症),后期结合临床表现及基因检测结果,确诊为PGK 1缺乏。结论磷酸甘油酸激酶缺乏症是一类罕见的X连锁隐性遗传病,由PGK 1基因变异所致,该变异未见报道,扩充了Ⅸ型糖原累积病基因变异数据库。

Objective To explore the clinical features and diagnosis of the typeⅨglycogen accumulation disease(phosphoglyceric acid kinase 1 deficiency)resulted from PGK1 mutation.Methods Clinical traits,laboratory test results,and gene mutation screening by next-generation sequencing of a pediatric case with phosphoglyceric acid kinase 1 deficiency admitted to our hospital were retrospectively analyzed.Results A 3 years and 11 months old boy firstly came to our hospital for a sudden twitching onset,followed by rapid progression.He was attacked by recurrent twitching along with hemolytic anemia.During the third hospitalization,the boy developed the symptom of severe rhabdomyolysis,accompanied by obvious retardation of intelligence and motor developments.Genetic screening found a novel missense mutation(c.150C>G,p.Cys50Trp)in PGK 1 which was inherited from his mother.According to ACMG guideline,the mutation can be classified as“likely pathogenic”.The boy was diagnosed with PGK 1 deficiency based on the clinical traits and genetic test results.Conclusion The phosphoglycerate kinase deficiency was a kind of rare X-linked recessive genetic disease caused by PGK 1 mutation,which can be confirmed by clinical features combing the result of PGK 1 gene mutation.To our knowledge,this mutation is first reported and meaningful for expanding the genetic mutation spectrum of PGK 1.