Schuh S, Rosenblatt D S, Cooper B A, Schroeder M L, Bishop A J, Seargeant L E, Haworth J C
N Engl J Med. 1984 Mar 15;310(11):686-90. doi: 10.1056/NEJM198403153101104.
We describe an inborn error of vitamin B12 metabolism in an infant who had severe developmental delay, megaloblastic anemia, and homocystinuria. There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12. Treatment with hydroxocobalamin, but not with cyanocobalamin and folic acid, resulted in rapid clinical and biochemical improvement. Cultured fibroblasts showed an absolute growth requirement for methionine, defective incorporation of radioactivity from [14C]5-methyltetrahydrofolate into protein, and normal incorporation of radioactivity from [14C]propionate, thus assigning the intracellular defect to methionine synthesis. The proportion of intracellular methylcobalamin in the fibroblasts was decreased, but that of 5'-deoxyadenosylcobalamin was normal. Methionine synthetase activity in cell extracts was normal, as was cobalamin incorporation into cultured cells. This defect differs from those described previously in being limited to methylcobalamin accumulation and defective use of 5-methyltetrahydrofolate by intact cells with normal activity of methylmalonyl CoA mutase.
我们描述了一名患有严重发育迟缓、巨幼细胞贫血和高胱氨酸尿症的婴儿体内维生素B₁₂代谢的先天性缺陷。没有甲基丙二酸尿症或叶酸或维生素B₁₂缺乏的证据。用羟钴胺素治疗可使临床和生化指标迅速改善，而用氰钴胺素和叶酸治疗则无效。培养的成纤维细胞显示对蛋氨酸有绝对生长需求，[¹⁴C]5-甲基四氢叶酸的放射性掺入蛋白质存在缺陷，而[¹⁴C]丙酸盐的放射性掺入正常，因此将细胞内缺陷归因于蛋氨酸合成。成纤维细胞内甲基钴胺素的比例降低，但5'-脱氧腺苷钴胺素的比例正常。细胞提取物中的蛋氨酸合成酶活性正常，钴胺素掺入培养细胞的情况也正常。这种缺陷与先前描述的不同，它仅限于甲基钴胺素积累以及完整细胞对5-甲基四氢叶酸的利用存在缺陷，而甲基丙二酰辅酶A变位酶活性正常。
