甲基丙二酸血症cblA型12例分析

目的探讨甲基丙二酸血症(methylmalonic acidemia,MM A)cblA型患儿的临床特点、基因变异类型及治疗效果。方法分析12例cblA型MMA患儿的临床表现,治疗方案及预后,对先证者及其父母进行MMAA基因的变异分析。结果MMA cblA型患儿主要表现为呕吐、气促和嗜睡。维生素B12治疗对11例(91.7%)患儿有效。治疗后患儿血丙酰肉碱、丙酰肉碱与乙酰肉碱比值、尿甲基丙二酸及甲基枸椽酸水平均显著降低,差异有统计学意义(均P<0.05)。8例患儿生长发育正常(66.7%),4例智力运动发育落后(33.3%)。检测到14种MMAA基因变异,包括6种新变异:c.54delA(p.A19Hfs*43)、c.275G>A(p.G92V)、c.456delT(p.G153Vfs*8)、c.667dupA(p.T223Nfs*4)、c.1114C>T(p.Q372X)和c.1137_1138delCA(p.F379Lfs*27)e最常见的变异为c・365T>C(p.L122P)(29.2%)。结论cblA型MMA患儿主要表现为呕吐、气促和嗜睡,大部分患儿为维生素B12治疗有效型。c.365T>C为中国MMAA基因的常见变异。

Analysis of 12 cases with methylmalonicacidemia cblA type

Objective To explore the clinical feature»genetic variant and clinical outcome of patients with cblA-type methylmalonic acidemia(MMA).Methods Clinical manifestations,therapeutic schedule and prognosis of 12 patients with cblA-type MMA were analyzed.MMAA gene variants were analyzed for all patients and their parents.Results Vomiting,dyspnea and drowsiness were the major clinical features of cblA-type MMA.Eleven patients were vitamin Bi2-responsive.After treatment,the blood level of propionylcarnitine,ratio of propionylcarnitine/acetylcarnitine,urine level of methylmalonic acid and methylcitric acid have decreased significantly(PV0.05).Follow-up study showed that 8 patients(66.7%)had normal development,while the rest(33.3%)remained to have various level of mental or movement delay.Fourteen MMAA gene variants were detected,with c.365T>C(p.L122P)being the most common(29.2%).Six novel variants,including c.54delA(p.A19Hfs*43),c.2750 A(p.G92V),c.456delT(p.G153Vfs*8),c.667dupA(p.T223Nfs*4),c.11140 T(p.Q372X)and c.1137_1138delCA(p.F379Lfs*27)were found.Conclusion The main clinical manifestations of patients with cblA-type of MMA include vomiting,dyspnea and drowsiness.Most patients are vitamin Bi2-responsive,c.365T>C is a potential hot spot variant of MMAA gene in China.