新生儿甲基丙二酸血症的临床特点分析

Clinical characteristics of methylmalonic acidemia during neonatal period

目的总结新生儿甲基丙二酸血症患儿的临床与实验室特点。方法分析2008-2016年我院NICU收治的21例新生儿甲基丙二酸血症患儿的临床表现、诊治经过、生化特点及基因资料,并对治疗效果进行随访。结果 21例患儿中甲基丙二酸血症合并同型半胱氨酸血症6例(28.6%),其中2例甲基丙二酸血症合并同型半胱氨酸血症患儿接受了基因检测,证实为Cbl C缺陷。21例患儿中最常见的临床表现依次为喂养困难(16例)、反应弱(13例)、惊厥(7例)、发热(3例);化验检查见高氨血症(11例)、代谢性酸中毒(10例)、大细胞贫血(8例)、粒细胞减低(7例)、血小板减少(7例)、肝功能异常(3例)。初步诊断仅有3例被考虑为先天性遗传代谢病。确诊后共有11例患儿接受了维生素B12、左卡尼汀、特殊饮食或甜菜碱治疗。21例患儿中7例失访,6例死亡,7例遗留轻-重度智力体力发育障碍,1例生长发育基本正常。结论新生儿甲基丙二酸血症临床表现及实验室检查缺乏特异性,可以三系减低或两系减低为突出表现,易误诊,致死率、致残率高。合并高同型半胱氨酸血症多见,与单纯型甲基丙二酸血症治疗方法不同。

Objective To summarize the clinical and laboratory characteristics of methylmalonic acidemia during neonatal period. Methods Totally 21 neonates diagnosed with methylmalonic aeidemia were hospitalized in the NICU from 2008 to 2016. The clinical manifestations, diagnosis, treatment and biochemical features were collected and analyzed. Gene test was performed in 2 cases. All of the patients were followed up. Results Six（28.6%） of 21 cases were methylmalonic acidemia combined with homocysteinemia, of which, 2 cases were confirmed to be CblC defect by gene test. The common clinical manifestations were feeding difficulty（ 16 cases） , weakness （ 13 cases ） , seizure （ 7 cases ） , and fever （ 3 cases）. Laboratory findings showed hyperammonemia （ 11 cases ） , metabolic aci- dosis （ 10 cases） , megaloblastic anemia （ 8 cases ） , neutropenia （ 7 cases ） , thrombocytopenia （ 7 cases ） , and liver dysfunction （ 3 ca- ses ）. Only 3 patients were admitted with suspected inborn errors of metabolism. Totally 11 cases were treated with eobalamin, L-carnitine, special diet or betaine. Among 21 cases, 7 cases were loss of follow-up, 6 cases died, 7 cases had mild to severe mental retardation, and 1 case had normal mental and physical development. Conclusion The clinical manifestations and laboratory findings of neonatal methylmalonic acidemia are lack of specificity, manifested with thromboeytopenia, ncutropenia or erythropenia. It is easy to be misdiagnosed, with high mortality and morbidity rate. Mcthylmalonic acidemia combined with homocystcincmia is common, but the treatment is different from isolated MMA.