CAJ | 학술논문

目的报道1个以脑血管病为主要临床表现的晚发型Pompe病家系,总结其临床、病理和分子遗传学特点.方法对1个伴脑血管病的兄妹共患病晚发型Pompe病家系进行家系调查和临床、病理资料收集；5名家系成员均行酸性α-糖苷酶(GAA)基因目的片段PCR扩增与测序.结果患病者为兄妹2人,均有自青少年期出现的进行性肢带肌无力,近来出现眩晕、共济失调等症状方就诊,颅脑CT和MRI示梗死、出血和脑白质多发缺血变性灶,其中哥哥颅脑CT血管成像(CTA)示脑动脉多处狭窄与后循环系统多发动脉瘤,妹妹颅脑CTA仅显示有多处动脉串珠样狭窄.前者肌肉活体组织检查病理表现为典型的空泡样变性和肌纤维内糖原的沉积.2例患者GAA酶活性均明显低于正常.对该家系5位家族成员(包括2例患者)的GAA基因分析发现2例患者及其母亲存在第9号外显子自1388位点起19个碱基的杂合缺失突变.结论以后循环受累为主的脑血管病是Pompe病少见的特殊表型.GAA基因c.1388 del 19为新发突变,与临床表型的关系尚不能确定.
목적 보도1개이뇌혈관병위주요림상표현적만발형Pompe병가계,총결기림상、병리화분자유전학특점.방법 대1개반뇌혈관병적형매공환병만발형Pompe병가계진행가계조사화림상、병리자료수집；5명가계성원균행산성α-당감매(GAA)기인목적편단PCR확증여측서.결과 환병자위형매2인,균유자청소년기출현적진행성지대기무력,근래출현현훈、공제실조등증상방취진,로뇌CT화MRI시경사、출혈화뇌백질다발결혈변성조,기중가가로뇌CT혈관성상(CTA)시뇌동맥다처협착여후순배계통다발동맥류,매매로뇌CTA부현시유다처동맥천주양협착.전자기육활체조직검사병리표현위전형적공포양변성화기섬유내당원적침적.2례환자GAA매활성균명현저우정상.대해가계5위가족성원(포괄2례환자)적GAA기인분석발현2례환자급기모친존재제9호외현자자1388위점기19개감기적잡합결실돌변.결론 이후순배수루위주적뇌혈관병시Pompe병소견적특수표형.GAA기인c.1388 del 19위신발돌변,여림상표형적관계상불능학정.
Objective To report a pedigree with late-onset Pompe' s disease complicated with cerebral vascular diseases as to summarize their clinical,pathological and molecular genetic characteristics.Methods We investigated the clinical and pathological data of the two affected siblings with late-onset Pompe' s disease complicated with cerebral vascular diseases.All the 5 members of this pedigree accepted the GAA gene analysis.Results Both affected siblings had progressive pelvic girdle muscle weakness from young adult age,and recently developed vertigo and ataxia.Brain imaging of them revealed multiple cerebral hemorrhage,infarction and diffuse ischemic white matter lesions.The brother had multiple aneurysms and stenoses of cerebral arteries revealed by brain CTA.However,his sister was only found to have multi-beaded stenoses of cerebral arteries.The muscle pathology of the brother showed typical vacuolar degeneration and glycogen storage in muscle fibers. The GAA enzyme activity of 2 siblings were dramatically lower than normal.A heterozygous 19 bp-deletion (c.1388-c.1406,exon 9) were found in GAA gene in the 2 siblings and their healthy mother. Conclusions Cerebrovascular involvement should be a special phenotype of Pompe' s disease.A novel heterozygous mutation c.1388del19 in GAA gene was found in this pedigree,but the relationship between the mutation and the rare clinical phenotype needs further study.