CAJ | 학술논문

目的分析6例婴儿型糖原累积症Ⅱ型(glycogen storage disease typeⅡ,GSDⅡ)的临床特点.方法回顾性分析2012年1月-2014年6月北京大学第一医院儿科诊断的6例婴儿型GSDⅡ患儿的临床资料.对其临床特点、血生化检查、胸部X线片、超声心动图、心电图、酸性α-葡糖苷酶(GAA)活性检查、GAA基因突变分析结果进行分析.结果 6例婴儿型GSDⅡ患儿有5例诊断为经典婴儿型(男1例,女4例),1例女性患儿为非经典婴儿型.起病年龄从生后到3个月不等,所有患儿均表现出不同程度的肌无力、肌张力低下,运动发育落后甚至倒退,还表现有呼吸困难(4例)、喂养困难(2例),哭声弱(2例)、肝脏增大(2例)、巨舌(1例).6例均有心界扩大,3例胸部X线发现心影增大,心胸比例增加,4例行超声心动图均有心肌肥厚表现,3例行心电图检查均有PR间期缩短及心室高电压表现.所有患儿的血清肌酸激酶水平较正常升高3～7倍(441 ～1 238 U/L).4例进行GAA活性检查的患儿的酶活性水平均较参考值明显降低[1.3～2 nmol/(spot· d)].4例进行GAA基因检测,共有8种不同的点突变;其中错义突变6种,分别是c.998C＞ A(p.Thr333Lys)、c.1280T＞C(p.Met427Thr)、c.1760T＞C(p.Leu587Pro)、c.1924G＞ T(p.Val642Phe)、c.2012T＞A(p.Met671Lys)、c.2105G＞ A(p.Arg702His);无义突变1种,c.2662G＞ T(p.Glu888X);移码突变1种,c.2812_2813delTG(p.Cys938fs).随访中5例经典婴儿型患儿已死亡,死亡年龄7个月～1岁10个月,平均生存时间14.5个月;1例非经典型患儿仍存活,现已2岁5个月.结论婴儿型GSDⅡ临床主要表现有肌无力、肌张力低下,心肌受累;血清肌酸激酶水平升高、GAA活性明显降低.GAA基因检出致病突变.
목적 분석6례영인형당원루적증Ⅱ형(glycogen storage disease typeⅡ,GSDⅡ)적림상특점.방법 회고성분석2012년1월-2014년6월북경대학제일의원인과진단적6례영인형GSDⅡ환인적림상자료.대기림상특점、혈생화검사、흉부X선편、초성심동도、심전도、산성α-포당감매(GAA)활성검사、GAA기인돌변분석결과진행분석.결과 6례영인형GSDⅡ환인유5례진단위경전영인형(남1례,녀4례),1례녀성환인위비경전영인형.기병년령종생후도3개월불등,소유환인균표현출불동정도적기무력、기장력저하,운동발육락후심지도퇴,환표현유호흡곤난(4례)、위양곤난(2례),곡성약(2례)、간장증대(2례)、거설(1례).6례균유심계확대,3례흉부X선발현심영증대,심흉비례증가,4례행초성심동도균유심기비후표현,3례행심전도검사균유PR간기축단급심실고전압표현.소유환인적혈청기산격매수평교정상승고3～7배(441 ～1 238 U/L).4례진행GAA활성검사적환인적매활성수평균교삼고치명현강저[1.3～2 nmol/(spot· d)].4례진행GAA기인검측,공유8충불동적점돌변;기중착의돌변6충,분별시c.998C＞ A(p.Thr333Lys)、c.1280T＞C(p.Met427Thr)、c.1760T＞C(p.Leu587Pro)、c.1924G＞ T(p.Val642Phe)、c.2012T＞A(p.Met671Lys)、c.2105G＞ A(p.Arg702His);무의돌변1충,c.2662G＞ T(p.Glu888X);이마돌변1충,c.2812_2813delTG(p.Cys938fs).수방중5례경전영인형환인이사망,사망년령7개월～1세10개월,평균생존시간14.5개월;1례비경전형환인잉존활,현이2세5개월.결론 영인형GSDⅡ림상주요표현유기무력、기장력저하,심기수루;혈청기산격매수평승고、GAA활성명현강저.GAA기인검출치병돌변.
Objective To summarize clinical features and diagnosis of Chinese infantile patients with glycogen storage disease type Ⅱ (GSD Ⅱ).Method Six infant patients with GSD Ⅱ diagnosed from January 2012 to June 2014 in the Department of Pediatrics,Peking University First Hospital were enrolled into this study.Clinical information of the 6 patients,including clinical manifestation,blood biochemistry,chest X-ray,echocardiogram,electrocardiogram,acid alpha-glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of polymerase chain reaction (PCR) product were reviewed.Result Of the 6 patients,five were female and one was male,five of whom were classic infantile type while the other one was atypical.The age of onset ranged from birth to 3-month-old.All patients had varying degrees of generalized muscle weakness,hypotonia and development retardation or retrogression.Other common findings were feeding difficulties in two patients,tongue weakness in two patients,respiratory distress in four patients,macroglossia in one patient,and hepatomegaly in two patients.Left ventricular hypertrophy and cardiomegaly were obvious in all the six patients.All six patients were found to have a enlarged heart in physical examination,and three patients who underwent a chest X-ray examination had an enlarged heart shadow.Four patients who had an echocardiography were found to have myocardial hypertrophy.The electrocardiogram in three patients showed short PR intervals and high voltage.The creatine kinase (CK) levels were three to seven times elevated.The mildest elevated CK was 441 IU/L,and the highest CK level was 1 238 U/L.Assay of GAA enzyme activity in whole blood showed significantly reduced activity (1.3 nmol/(spot · d) to 2 nmol/(spot · d)) in the patients tested.Gene sequencing in 4 patients showed 8 pathogenic mutations,including 6 missense mutations,one nonsense mutation and one frameshift mutation.The missense mutations were c.998C ＞ A(p.Thr333Lys),c.1280T ＞ C(p.Met427Thr),c.1760T ＞ C (p.Leu.587Pro),c.1924G ＞ T(p.Val642Phe),c.2012T ＞ A(p.Met671Lys) and c.2105G ＞ A (p.Arg702His).The nonsense mutation was c2662G ＞ T(p.Glu888X),and the frameshift mutation was c2812 _2813delTG(p.Cys938fs).The 5 classic infantile patients died at the age of 7 to 22 months.The atypical infantile patient was 2 years and five months old according to our latest follow up.Conclusion Infantile GSD Ⅱ had similar motor manifestations and cardiac involvements,blood biochemical test,imaging findings,enzyme assays,though there were slight differences.The probability of GSD Ⅱ should be taken into consideration if an infant has both muscular disease and cardiac involvement.