Mamlok R J, Isenberg J N, Rassin D K, Norcross K, Tallan H H
Neuropediatrics. 1986 May;17(2):94-9. doi: 10.1055/s-2008-1052508.
We have identified a patient with methylmalonic aciduria and homocystinuria due to a defect in cobalamin metabolism of the cb1C type mutant. At the time of admission at eight months of age the patient was malnourished, hypotonic and had macrocytic anemia. Neonatal screening for hypermethioninemia associated with homocystinuria had been normal. Serum vitamin B12 was markedly increased and folate concentration was above normal, as were urinary homocystine and methylmalonic acid. The patient had abnormal brain stem auditory and visual evoked potentials. Fibroblast activity of N5-methyltetrahydrofolate: homocysteine methyltransferase was reduced to approximately 10% of concurrent controls. A course of therapy with hydroxocobalamin resulted in a 90% reduction in excretion of methylmalonic acid and normalization of the evoked potentials. These studies support the efficacy of hydroxocobalamin therapy in this disease, suggest that methylmalonic acid may be the most appropriate metabolite to monitor for therapeutic response, and in importance of electrophysiologic studies in character in objectively monitoring the response to treatment metabolic disease.
我们发现了一名因cb1C型突变导致钴胺素代谢缺陷而患有甲基丙二酸尿症和高胱氨酸尿症的患者。该患者八个月大入院时营养不良、肌张力减退且患有大细胞性贫血。新生儿高甲硫氨酸血症合并高胱氨酸尿症筛查结果正常。血清维生素B12显著升高，叶酸浓度高于正常水平，尿高胱氨酸和甲基丙二酸水平也是如此。患者脑干听觉和视觉诱发电位异常。N5-甲基四氢叶酸：高半胱氨酸甲基转移酶的成纤维细胞活性降至同期对照的约10%。羟钴胺素治疗疗程使甲基丙二酸排泄减少90%，诱发电位恢复正常。这些研究支持了羟钴胺素治疗该疾病的疗效，表明甲基丙二酸可能是监测治疗反应的最合适代谢物，以及电生理研究在客观监测代谢疾病治疗反应方面的重要性。
