迟发型甲基丙二酸尿症三例临床和影像学分析

目的探讨迟发型甲基丙二酸尿症的临床和影像学特点及其病理生理机制。方法运用尿有机酸分析(气相色谱-质谱联用)进行筛查与诊断，对3例(男2例、女1例)迟发型甲基丙二酸尿症患者的临床经过、生化特点、影像学表现、诊疗情况进行分析。结果3例患者均因神经系统损害起病。例1于24岁发病，出现间断遗尿及进行性加重的智能和运动障碍，四肢力弱、肌张力呈铅管样增高、双侧锥体束征阳性。例2于13岁起学习困难，智力下降，走路不稳，伴视力减退，16岁时出现惊厥发作1次。两例患者均合并肾损害，脑电图异常，脑MRI显示双侧大脑白质广泛长T2信号及弥漫性脑萎缩，血浆同型半胱氨酸浓度明显升高、左旋肉碱降低。例3为34岁女性，走路不稳、乏力2个月余，双下肢力弱，深感觉消失，四肢肌张力增高，腱反射消失，化验显示中度大细胞性贫血、维生素B12缺乏，血浆同型半胱氨酸浓度正常，脑MRI示双侧苍白球、内囊后肢和大脑脚长T2信号。3例患者尿甲基丙二酸、甲基枸橼酸浓度均显著升高，经维生素B12治疗后症状迅速改善。结论3例患者均符合迟发性甲基丙二酸尿症维生素B12反应型诊断。例1、2合并同型半胱氨酸血症，患者临床表现和影像学改变的差异可能与生化类型有关。本型患者经维生素B12疗效显著，预后良好，对成年发病的脑变性病患者应注意本症的鉴别诊断。

Clinical and radiological features of the late-onset methylmalonic aciduria:a review of three cases

jective To study the clinical and radiological features of the patients with late-onset methylmalonic aciduria ( MMA). Methods Two men and one woman with MMA were screened and confirmed by urinary organic acid analysis with gas chromatograph/mass spectrometer (GC/MS) at their 26, 18 and 34 years old, respectively. Their clinical features, laboratory findings, radiological manifestations, treatment and outcome were reviewed. Results The clinical features of 3 patients were varied with neurological abnormalities. Case 1 had periodic enuresis for 16 months, progressive dementia and movement disorder for 3 months. Physical examination showed an apparent cognitive decline with psychiatric symptoms. Dysarthria, bilateral weakness and pyramidal signs, rigidity and mild tremor of limbs were observed. Case 2 had a progressive memory deterioration, learning difficulty, walking unstably and decreased vision when he was 13 years old, and a general seizure at an age of 16 years. Diffused abnormalities of EEG and rnild renal defects were found in the above two patients. General white matter hyperintensity and cerebral atrophy on T2-weighted MR images were evident. Additionally, these two patients had hyperhomocystinemia and carnitine deficiency. Case 3 had complained about walking unstably and fatigue over 2 months. Reduced facial movements, deep sensation loss and muscle weakness in lower extremities, marked rigidity and diminished tendon reflexes were detected. Megaloblastic anemia and cobalamin deficiency were found. MRJ performed revealed bilateral symmetric areas having high density involving the globi pallidi, posterior limbs of internal capsule and the cerebral peduncles. Remarkable elevations of urinary methylmalonic and methylcitric acid were confirmed in all 3 patients. After vitamin B12 supplementation, significant improvement was observed. Conclusion Three cases with vitamin BI2 responsive type of late-onset MMA were reported. Two patients were combined with hyperhomocystinemia and the other had only isolated MMA. There might remain prominent differences among MMA subgroups in clinical presentations and neuroradiologic findings. Vitamin B12 might be very effective to improve the prognosis of the patients. MMA should be considered as a differential diagnosis for the etiological investigation of adult cerebral metabolic or degenerative diseases.