摘要
目的 分析婴儿型Pompe病所致肥厚型心肌病2例患儿的临床及GAA基因突变结果.方法 收集一个家系中2例婴儿型Pompe病患儿的临床资料,采用于血滤纸片法检测外周血白细胞酸性α-葡萄糖苷酶(GAA)活性,PCR扩增GAA基因编码区,并直接测序分析GAA基因突变.结果 同胞兄妹的2例患儿,于4~5个月大时出现舌大、呼吸困难、肌力减低、心肌肥厚,血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肌酸激酶、肌酸激酶同工酶、乳酸脱氢酶、羟丁酸脱氢酶升高;2例患儿外周血GAA活性均明显低于正常;基因测序分析发现2例患儿GAA基因存在两个复合杂合性突变:c.1822C>T和c.2297A>C,该两种突变均尚未在大陆地区患者中发现,前者已经被证实具有致病性,后者为尚未报道的新突变类型.结论 GAA基因复合杂合性突变c.1822C>T和c.2297A>C可导致患儿出现以肥厚型心肌病为特征的经典婴儿型Pompe病,DBS法检测外周血GAA活性及GAA基因检测是可行、有效的诊断方法.
Objective To analyze the clinical characteristic and identify the gene mutation in a family with hypertrophic cardiomyopathy,likely due to infantile Pompe disease.Methods Clinical data of two infants with hypertrophic cardiomyopathy in a family were collected.Peripheral leukocytes were collected from vein blood.Activity of acidα-glucosidase(GAA)in leukocytes were measured.The coding region of GAA gene was amplified by polymerase chain reaction,and then directly sequenced.Results Two infants from the same family were presented with mild macroglossia,dyspnea,generalized hypotoni,and hypertrophic cardiomyopathy at 4-5 months of age.The serum alanine aminotransferase,glutamic-oxaloacetic transaminase,creatine phosphokinase,creatine kinase-MB,lactate dehydrogenase,and hydroxybutyrate dehydrogenase was elevated.The GAA activities in leukocytes in the two infants were significantly lower than in normal controls.Gene sequencing revealed that two compound heterozygous mutations,c.1822C>T and c.2297A>C,in the two infants.To date,it was the first report for the two mutations in the GAA gene in the China's Mainland.The mutation c.1822C>T had been reported to be pathogenic,and the latter one,c.2297A>C,was a new mutation.Conclusions The compound heterozygous c.1822C>T and c.2297A>C mutations in GAA gene caused the classic infantile Pompe disease characterized by hypertrophic cardiomyopathy.Determination of GAA activity in peripheral leukocytes and GAA gene sequencing were effective and feasible methods for the diagnosis ofGSDⅡ.
作者
崔英华
王欣
王青雷
蓬淑超
闫波
Cui Yinghua;Wang Xin;Wang Qinglei;Peng Shuchao;Yan Bo(Division of Cardiology,Affiliated Hospital of Jining Medical University,Jining Medical University,Jining 272100,China)
关键词
糖原贮积病Ⅱ型
Pompe病
基因
点突变
Glycogen storage disease typeⅡ
Pompe disease
Genes
Point mutation
