目的对中国大陆地区婴儿期起病的早发型糖原贮积症Ⅱ型患者进行临床分析、基因突变分析及产前基因诊断。方法对2例婴儿期起病的糖原贮积症Ⅱ型患儿进行临床分析,并提取患儿及其父母的外周血DNA,应用聚合酶链反应(PCR)扩增α-1,4-葡萄糖苷酶基因(GAA)的19个外显子,直接测序,进行先证者及其父母的基因突变检测;在明确先证者基因突变后,对胎儿进行产前基因诊断。结果家系中2例患儿的发病时间均较早(第一胎男孩为1月+,第二胎女孩为2月),临床主要表现为心脏和骨骼肌受损的征象,以心肌和呼吸肌受累最为明显,患儿表现为明显的四肢肌张力低下,呼吸急促,口唇发绀,辅助检查提示患儿肌酸肌酶升高,胸部正位X片示心影增大,以心室为主,心脏超声示心脏明显增大,心肌肥厚。突变检测:GAA基因测序发现该家系先证者存在2个突变,分别为错义突变c.1935C>A(D645E)和无义突变c.1822C>T(R608*),其中后者为新突变,50例健康人对照100个等位基因测序未发现该位点的突变;羊水细胞GAA基因检测未发现该家系上述2个位点突变。结论婴儿期起病的糖原贮积症Ⅱ型患儿临床表现均较为严重,死亡率高,主要死亡原因为呼吸肌和心肌受累所导致的呼吸、心脏功能衰竭。本研究对一个糖原贮积症Ⅱ型家系进行了临床分析和基因诊断,明确了先证者发病的遗传学病因,并发现了一个新突变,为这个家庭的产前诊断和最终健康孩子的出生,打下了坚实的基础。 Objective To analyze the clinical features, gene mutation analysis and prenatal diagnosis of early onset glycogen storage disease type Ⅱ in infancy in mainland China. Methods Two cases of type 2 infants with glycogen storage disease that had onset in infancy were analyzed clinically. Peripheral blood DNA was extracted from children and their parents. Polymerase chain reaction (PCR) was used to amplify α-1,4- Nineteen exons of glucosidase gene (GAA) were sequenced directly for gene mutation testing of probands and their parents. Prenatal genetic diagnosis of the fetus was performed after identification of proband gene mutations. Results The onset time of two cases of pedigrees was earlier (the first-born boy was + month and the second-born girl was February). The clinical manifestations were heart and skeletal muscle injury signs, myocardial and respiratory muscles The most obvious involvement, the performance of children with obvious limb muscle tension, shortness of breath, cyanosis lips, assisted examination showed elevated creatine kinase in children, X-ray showed chest X-ray showed increased ventricular, heart-based, Show heart increased significantly, myocardial hypertrophy. Mutation detection: GAA gene sequencing found that there were two mutations in the probands of the pedigree, namely the missense mutation c.1935C> A (D645E) and the nonsense mutation c.1822C> T (R608 *), of which the latter was a new mutation No mutation was found in 100 alleles of 50 healthy controls. The GAA gene of amniotic fluid cells showed no mutation in the above two loci. Conclusion The onset of infantile glycogen storage disease type Ⅱ children are more serious clinical manifestations, the mortality rate is high, the main cause of death due to respiratory muscle and myocardial involvement caused by respiratory failure, heart failure. This study conducted a clinical analysis and genetic diagnosis of a Glycogen Storage Type 2 pedigree, identified the genetic cause of the proband’s onset, and found a new mutation for the prenatal diagnosis and eventual health of the child Born, laid a solid foundation.