Hallam L J, Sawyer M, Clark A C, Van der Weyden M B
Blood. 1987 Apr;69(4):1128-33.
We present findings on an infant with neonatal megaloblastic anemia, homocystinuria, and neurologic dysfunction that included developmental delay and tonic seizures. There was no methylmalonic aciduria. Cyanocobalamin therapy was accompanied by complete hematologic and neurologic recovery, diminished homocystine excretion, and subsequently normal neurologic development. Cultured fibroblasts and lymphoblasts showed a reduced methionine synthase activity and a growth requirement for methionine. Cobalamin incorporation by the patient's lymphoblasts was normal, but the proportion of cellular methylcobalamin in the patient's lymphoblasts and fibroblasts were markedly reduced and that of adenosylcobalamin normal. The reduced methionine synthase activity was independent of assay reducing (thiol) conditions, but normal levels of activity accompanied culture of the patient's lymphoblasts in medium with markedly increased cobalamin concentration. The characteristics of the reduced methionine synthase of our patient differ significantly from that of the previously described infant with cobalamin E disease and suggest that genetic heterogeneity may characterize this mutation.
我们报告了一名患有新生儿巨幼细胞贫血、同型胱氨酸尿症和神经功能障碍（包括发育迟缓和平直性癫痫）的婴儿的研究结果。不存在甲基丙二酸尿症。氰钴胺素治疗后，血液学和神经功能完全恢复，同型胱氨酸排泄减少，随后神经发育正常。培养的成纤维细胞和淋巴细胞显示甲硫氨酸合酶活性降低，且对甲硫氨酸有生长需求。患者淋巴细胞对钴胺素的摄取正常，但患者淋巴细胞和成纤维细胞中细胞甲基钴胺素的比例显著降低，而腺苷钴胺素的比例正常。甲硫氨酸合酶活性降低与检测还原（硫醇）条件无关，但在钴胺素浓度显著增加的培养基中培养患者淋巴细胞时，活性水平正常。我们患者甲硫氨酸合酶降低的特征与先前描述的患有钴胺素E病的婴儿有显著差异，提示该突变可能具有遗传异质性。
