CAJ | 학술논문

目的探讨1例临床疑似糖原累积病Ⅱ型患儿的临床特点和酸性-α-葡萄糖苷酶(GAA)基因突变情况.方法分析患儿病史,并检测患儿及其父母外周血白细胞酸性-α-葡萄糖苷酶活性,聚合酶链反应(polymerase chain reaction,PCR)扩增GAA编码区,直接测序分析GAA基因突变情况.结果该患儿生后2个月即出现喂养困难和全身肌无力,4个月发现心脏增大,6个月时死于心肺功能衰竭.患儿白细胞酸性-α-葡萄糖苷酶活性明显降低,仅为正常对照中位数的17.3%.DNA测序分析显示患儿携带一个新无义突变p.W738X和一个已报道的p.E888X突变.患儿及其母亲均携带假性缺陷等位基因c.1726G ＞ A;2065G ＞ A.结论 GAA酶活性测定结合基因诊断明确诊断1例临床疑似糖原累积病(GSD)Ⅱ型,发现1个GAA基因新无义突变p.W738X.根据患儿临床表现可诊断为婴儿型GSD Ⅱ,推测p.W738X突变对GAA酶活性影响严重.由于假性缺陷等位基因c.1726G ＞ A;2065G ＞ A可引起正常人GAA酶活性降低,故GAA基因突变分析对明确GSDⅡ型患者的诊断及其家系的产前诊断有重要意义.
목적 탐토1례림상의사당원루적병Ⅱ형환인적림상특점화산성-α-포도당감매(GAA)기인돌변정황.방법 분석환인병사,병검측환인급기부모외주혈백세포산성-α-포도당감매활성,취합매련반응(polymerase chain reaction,PCR)확증GAA편마구,직접측서분석GAA기인돌변정황.결과 해환인생후2개월즉출현위양곤난화전신기무력,4개월발현심장증대,6개월시사우심폐공능쇠갈.환인백세포산성-α-포도당감매활성명현강저,부위정상대조중위수적17.3%.DNA측서분석현시환인휴대일개신무의돌변p.W738X화일개이보도적p.E888X돌변.환인급기모친균휴대가성결함등위기인c.1726G ＞ A;2065G ＞ A.결론 GAA매활성측정결합기인진단명학진단1례림상의사당원루적병(GSD)Ⅱ형,발현1개GAA기인신무의돌변p.W738X.근거환인림상표현가진단위영인형GSD Ⅱ,추측p.W738X돌변대GAA매활성영향엄중.유우가성결함등위기인c.1726G ＞ A;2065G ＞ A가인기정상인GAA매활성강저,고GAA기인돌변분석대명학GSDⅡ형환자적진단급기가계적산전진단유중요의의.
Objective To investigate the acid α glucosidase(GAA)gene mutations and clinical features of a Chinese patient exhibiting signs and symptoms of infantile glycogen storage disease type Ⅱ(GSD Ⅱ). Methods Clinical features of the patient were reviewed,and GAA activity in the patient＇s and her parents＇ whole leukocytes were measured. GAA coding regions were amplified by polymerase chain reaction(PCR),and analyzed by direct DNA sequencing. Results The patient showed feeding difficulties,generalized hypotonia and weakness starting at 2 months of age. Cardiomegaly and cardiomyopathy were found at 4 months. She died of cardiorespiratory failure at the age of 6 months. GAA activity in leukocytes was low in the patient(17.3% of the median normal range). Genotyping revealed the patient was a heterozygote for a novel nonsense mutation p.W738X and a previously reported nonsense mutation p.E888X. The reported pseudodeficiency allele c.1726G ＞ A;2065G ＞ Awas found in the patient and her mother. Conclusions Correct diagnosis was made for this patient by combination of GAA activity assay and genetic analysis. From the clinical course,this patient should be classified as infantile type of GSD Ⅱ,suggesting that the novel mutation p.W738X may have a damaging effect on the function of GAA. Pseudodeficiency allele found in this family highlights the importance of genetic analysis of GAA when performing diagnosis and prenatal diagnosis for the affected families,as this allele causes low GAA activity in normal individuals.