晚发型甲基丙二酸尿症的临床和实验室研究

Clinical and laboratory study of late onset methylmalo nic aciduria

目的总结晚发型甲基丙二酸尿症(MMA)的临床特点.方法对11例晚发型MMA患儿的临床表现、实验室检查结果、影像学及治疗情况进行分析.结果 11例发病年龄3岁5个月～14岁, 表现发作性呕吐、嗜睡者5例;惊厥8例;智力损害9例;运动障碍10例,其中6例双下肢无力,2例四肢无力,1例走路姿势异常,1例小脑共济失调;伴构音不清、肢体震颤各2例,遗尿3例, 贫血、肝脏大各2例.实验室检查:5例外周血红细胞平均体积(MCV)增大,3例血尿、蛋白尿, 4例肝功能异常,6例血乳酸升高.11例患儿气相色谱-质谱联用分析(GC-MS)结果显示尿甲基丙二酸水平均明显升高,其中3例伴血浆同型半胱氨酸浓度升高.10例EEG检查,8例异常.头颅MRI检查,8例异常,其中6例有脑萎缩.9例治疗初期进行了大剂量维生素B12(VB12)试验性治疗,证实均为VB12反应型.结论晚发型甲基丙二酸尿症可表现为多系统损害,但以神经系统损害为主,主要症状为运动障碍、智力低下、惊厥;确诊依靠GC-MS尿有机酸分析;多数患儿为VB12反应型.

Objectives To summary the clinical characteristic of l ate onset methylmalonic aciduria (MMA). Methods The clinical man ifestations, the results of laboratory examinations, cranial MRI and treatment o f 11 patients with late onset MMA were analyzed. Results The age of onset was from 3 years and 5 months to 14 years. 5 patients had the episodes of vomiting and lethargy, seizures in 8 patients, mental retardation in 9 patie nts. 10 patients had movement disorders, weakness of two legs in 6 cases, four l imbs weakness in 2 cases, abnormal walking posture and cerebellar ataxia in 1 ca se respectively. Dysarthria and tremor was present in 2 cases respectively. 3 pa tients had enuresis. Anemia and hepatomegaly was present in 2 patients respectiv ely. The laboratory examination showed that the peripheral blood MCV was enlarge d in 5 cases. Hematuria and proteinuria was present in 3 patients. Liver functio n was abnormal in 4 cases. 6 patients showed elevated plasma lactic acid. Remark able elevation of urinary methylmalonic acid concentration was confirmed in all patients by gas chromatography-mass spectrometry (GC-MS), and 3 of them were als o had elevated homocysteine in plasma. EEG was abnormal in 8 patients. Cranial M RI was abnormal in 8 patients, 6 of them showed cerebral atrophy. 9 patients wer e Vitamin B 12 responsive. Conclusion Late onset MMA manife sted multiple system damage, the nervous system is mainly involved. The movement disorder ,mental retardation and seizures were the common symptoms. The diagno sis of MMA depend on the analysis of urine organic acid by GC-MS. Most patients were Vitamin B 12 responsive.