中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2014年
11期
817-821
,共5页
线粒体疾病%甲基丙二酸%肌张力过低%基因,SUCLA2
線粒體疾病%甲基丙二痠%肌張力過低%基因,SUCLA2
선립체질병%갑기병이산%기장력과저%기인,SUCLA2
Mitochondrial diseases%Methylmalonic acid%Muscle hypotonia%Genes,SUCLA2
目的 总结SUCLA2相关脑肌病型线粒体DNA耗竭综合征一例的病例资料,并结合文献复习对该病临床特征进行分析.方法 对首都医科大学附属北京儿童医院神经内科2010年10月首诊,2013年11月明确诊断的SUCLA2相关脑肌病型线粒体DNA耗竭综合征患儿,其临床表现、实验室检查及基因检测结果进行总结,并以“SUCLA2”为检索词查阅CNKI数据库、万方数据库、PubMed数据库和HGMD(人类基因突变数据库)专业版(建库至2014年4月),将国外报道的24例SUCLA2基因突变导致的线粒体DNA耗竭综合征及本病例共25例临床资料进行总结分析.结果 (1)患儿为5岁9个月男孩,2岁3个月时主因“生后至今不能竖头、独坐”首次来我院就诊.患儿为其母亲第6次怀孕第2次生产,足月顺产,出生体重为2 400 g,生后即出现喂养困难、听力异常、肌张力低下、发育迟滞和生长迟缓.至就诊仍不能竖头、翻身和独坐,伴肌肉萎缩,吞咽咀嚼困难,咽部分泌物潴留,易患呼吸道感染,感染时病情危重,呼吸困难,伴有骨骼畸形及面部特征.患儿父母为姨表近亲结婚.实验室检查:血乳酸增高,尿代谢筛查提示甲基丙二酸轻度增高,血串联质谱分析提示酮症、乳酸水平升高,丙酰肉碱(C3)、丁二酰肉碱和(或)甲基丙二酰肉碱(C4DC)水平轻度升高;头颅MRI示双侧尾状核头部、壳核呈长T2信号,伴脑萎缩样改变.应用高通量测序技术发现SUCLA2 c.970G>A纯合错义突变.(2)结合国外报道的24例SUCLA2基因突变导致的线粒体DNA耗竭综合征以及本例患儿资料,25例患儿中男14例、女11例;23例在生后4个月之内发病.最常见的临床表现有肌张力低下、肌肉萎缩、发育迟滞,其次为听力损害、运动障碍、喂养困难、生长迟缓及眼睑下垂或眼外肌麻痹,惊厥少见.22例患儿中20例(90.9%)血乳酸升高;20例患儿进行尿代谢筛查17例提示甲基丙二酸轻度升高,血C3和C4DC轻度升高.头颅MRI为基底节受累和脑萎缩样改变,以双侧尾状核、壳核对称性病变为主.25例中19例来自欧洲,其中的13例来自法罗群岛,为SUCLA2 c.534+ 1G>A纯合突变.结论 SUCLA2相关脑肌病型线粒体DNA耗竭综合征临床特征为:生后或婴儿早期出现严重肌张力低下、喂养困难、生长迟缓、发育迟滞(尤其是运动)、听力损害等;血乳酸增高,尿甲基丙二酸轻度增高,血C3和C4DC轻度升高;头颅MRI为双侧对称性尾状核、壳核受累,伴有脑萎缩样改变.发现SUCLA2致病性突变可确诊.
目的 總結SUCLA2相關腦肌病型線粒體DNA耗竭綜閤徵一例的病例資料,併結閤文獻複習對該病臨床特徵進行分析.方法 對首都醫科大學附屬北京兒童醫院神經內科2010年10月首診,2013年11月明確診斷的SUCLA2相關腦肌病型線粒體DNA耗竭綜閤徵患兒,其臨床錶現、實驗室檢查及基因檢測結果進行總結,併以“SUCLA2”為檢索詞查閱CNKI數據庫、萬方數據庫、PubMed數據庫和HGMD(人類基因突變數據庫)專業版(建庫至2014年4月),將國外報道的24例SUCLA2基因突變導緻的線粒體DNA耗竭綜閤徵及本病例共25例臨床資料進行總結分析.結果 (1)患兒為5歲9箇月男孩,2歲3箇月時主因“生後至今不能豎頭、獨坐”首次來我院就診.患兒為其母親第6次懷孕第2次生產,足月順產,齣生體重為2 400 g,生後即齣現餵養睏難、聽力異常、肌張力低下、髮育遲滯和生長遲緩.至就診仍不能豎頭、翻身和獨坐,伴肌肉萎縮,吞嚥咀嚼睏難,嚥部分泌物潴留,易患呼吸道感染,感染時病情危重,呼吸睏難,伴有骨骼畸形及麵部特徵.患兒父母為姨錶近親結婚.實驗室檢查:血乳痠增高,尿代謝篩查提示甲基丙二痠輕度增高,血串聯質譜分析提示酮癥、乳痠水平升高,丙酰肉堿(C3)、丁二酰肉堿和(或)甲基丙二酰肉堿(C4DC)水平輕度升高;頭顱MRI示雙側尾狀覈頭部、殼覈呈長T2信號,伴腦萎縮樣改變.應用高通量測序技術髮現SUCLA2 c.970G>A純閤錯義突變.(2)結閤國外報道的24例SUCLA2基因突變導緻的線粒體DNA耗竭綜閤徵以及本例患兒資料,25例患兒中男14例、女11例;23例在生後4箇月之內髮病.最常見的臨床錶現有肌張力低下、肌肉萎縮、髮育遲滯,其次為聽力損害、運動障礙、餵養睏難、生長遲緩及眼瞼下垂或眼外肌痳痺,驚厥少見.22例患兒中20例(90.9%)血乳痠升高;20例患兒進行尿代謝篩查17例提示甲基丙二痠輕度升高,血C3和C4DC輕度升高.頭顱MRI為基底節受纍和腦萎縮樣改變,以雙側尾狀覈、殼覈對稱性病變為主.25例中19例來自歐洲,其中的13例來自法囉群島,為SUCLA2 c.534+ 1G>A純閤突變.結論 SUCLA2相關腦肌病型線粒體DNA耗竭綜閤徵臨床特徵為:生後或嬰兒早期齣現嚴重肌張力低下、餵養睏難、生長遲緩、髮育遲滯(尤其是運動)、聽力損害等;血乳痠增高,尿甲基丙二痠輕度增高,血C3和C4DC輕度升高;頭顱MRI為雙側對稱性尾狀覈、殼覈受纍,伴有腦萎縮樣改變.髮現SUCLA2緻病性突變可確診.
목적 총결SUCLA2상관뇌기병형선립체DNA모갈종합정일례적병례자료,병결합문헌복습대해병림상특정진행분석.방법 대수도의과대학부속북경인동의원신경내과2010년10월수진,2013년11월명학진단적SUCLA2상관뇌기병형선립체DNA모갈종합정환인,기림상표현、실험실검사급기인검측결과진행총결,병이“SUCLA2”위검색사사열CNKI수거고、만방수거고、PubMed수거고화HGMD(인류기인돌변수거고)전업판(건고지2014년4월),장국외보도적24례SUCLA2기인돌변도치적선립체DNA모갈종합정급본병례공25례림상자료진행총결분석.결과 (1)환인위5세9개월남해,2세3개월시주인“생후지금불능수두、독좌”수차래아원취진.환인위기모친제6차부잉제2차생산,족월순산,출생체중위2 400 g,생후즉출현위양곤난、은력이상、기장력저하、발육지체화생장지완.지취진잉불능수두、번신화독좌,반기육위축,탄인저작곤난,인부분비물저류,역환호흡도감염,감염시병정위중,호흡곤난,반유골격기형급면부특정.환인부모위이표근친결혼.실험실검사:혈유산증고,뇨대사사사제시갑기병이산경도증고,혈천련질보분석제시동증、유산수평승고,병선육감(C3)、정이선육감화(혹)갑기병이선육감(C4DC)수평경도승고;두로MRI시쌍측미상핵두부、각핵정장T2신호,반뇌위축양개변.응용고통량측서기술발현SUCLA2 c.970G>A순합착의돌변.(2)결합국외보도적24례SUCLA2기인돌변도치적선립체DNA모갈종합정이급본례환인자료,25례환인중남14례、녀11례;23례재생후4개월지내발병.최상견적림상표현유기장력저하、기육위축、발육지체,기차위은력손해、운동장애、위양곤난、생장지완급안검하수혹안외기마비,량궐소견.22례환인중20례(90.9%)혈유산승고;20례환인진행뇨대사사사17례제시갑기병이산경도승고,혈C3화C4DC경도승고.두로MRI위기저절수루화뇌위축양개변,이쌍측미상핵、각핵대칭성병변위주.25례중19례래자구주,기중적13례래자법라군도,위SUCLA2 c.534+ 1G>A순합돌변.결론 SUCLA2상관뇌기병형선립체DNA모갈종합정림상특정위:생후혹영인조기출현엄중기장력저하、위양곤난、생장지완、발육지체(우기시운동)、은력손해등;혈유산증고,뇨갑기병이산경도증고,혈C3화C4DC경도승고;두로MRI위쌍측대칭성미상핵、각핵수루,반유뇌위축양개변.발현SUCLA2치병성돌변가학진.
Objective To analyze the clinical characteristics of SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient,and review the latest clinical research reports.Method Clinical,laboratory and genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by department of Neurology,Beijing Children's Hospital in November,2013 were reported,and through taking "SUCLA2" as key words to search at CNKI,Wanfang,PubMed and the Human Gene Mutation Database (HGMD) professional to date,the clinical characteristics of 24 reported cases of SUCLA2-related encephalomyopathic MDS in international literature in combination with our case were analyzed.Result (1) The patient was 5 years and 9 months old,born as a term small for gestational age infant whose birth weight was 2 400 g,and presented since birth with severe muscular hypotonia,feeding difficulties,failure to thrive,psychomotor retardation and hearing impairment.Until now,he still showed severe developmental retardation,together with muscular atrophy,thoracocyllosis and scoliosis,and facial features.The patient is the first born from consanguineous healthy parents,whose relationship is cousins.Laboratory tests showed urinary excretion of mild methylmalonic acid (MMA),elevated plasma lactate concentration,and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling.MRI showed brain atrophy-like and bilateral T2 hyperintensities in bilateral caudate nuclei and putamen.By Next-Generation Sequencing (NGS),we identified a novel homozygous missense mutation (c.970G > A) in the SUCLA2 in a highly conserved amino acid residue.(2) The total number was only 25 with a male to female ratio of 14:11,and age of onset of 23 was 0-4 months.The most common clinical features in patients with SUCLA2 mutation were permanent hypotonia,muscle atrophy,psychomotor retardation and scoliosis or kyphosis.Frequent signs included hearing impairment,hyperkinesia,dystonia or athetoid movements,feeding difficulties,growth retardation and ptosis or ophthalmoplegia.Epilepsy was occasionally observed.The combination of lactic acidemia,mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling were characteristic markers.MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei).Nineteen patients originated from Europe,with 13 of whom originated from Faroe Islands that carry a homozygous mutation (c.534 + 1G > A) in SUCLA2.Conclusion SUCLA2-related encephalomyopathic MDS is characterized by onset of severe hypotonia in early infancy,feeding difficulties,growth retardation,psychomotor retardation and hearing impairment.Metabolic findings usually include lactic acidemia,mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester profiling.MRI showed brain atrophy-like and bilateral basal ganglia involvement (mainly the putamen and caudate nuclei).SUCLA2 pathogenic mutations would confirm the diagnosis.