Savage D G, Lindenbaum J, Stabler S P, Allen R H
Department of Medicine, Columbia University, College of Physicians and Sugeons, Columbia-Presbyterian Medical Center, New York, New York 10032.
Am J Med. 1994 Mar;96(3):239-46. doi: 10.1016/0002-9343(94)90149-x.
Patients with cobalamin (vitamin B12) deficiency usually lack many of the classic features of severe megaloblastic anemia; because of the low diagnostic specificity of decreased serum cobalamin levels, demonstrating the deficiency unequivocally is often difficult. We examined the sensitivity of measuring serum concentrations of methylmalonic acid and total homocysteine for diagnosing patients with clear-cut cobalamin deficiency and compared the results with those of patients with clear-cut folate deficiency.
Serum metabolites were measured for all patients seen from 1982 to 1989 at two university hospitals who met the criteria for cobalamin and folate deficiency states and for such patients seen from 1968 to 1981 from whom stored sera were available. In all, 406 patients had 434 episodes of cobalamin deficiency and 119 patients had 123 episodes of folate deficiency. Criteria for deficiency states included serum vitamin levels, hematologic and neurologic findings, and responses to therapy. Responses were documented in 97% of cobalamin-deficient patients and 76% of folate-deficient patients. Metabolite levels were measured by modified techniques using capillary-gas chromatography and mass spectrometry.
Most of the cobalamin-deficient patients had underlying pernicious anemia; two thirds were blacks or Latinos. Hematocrits were normal in 28% and mean cell volumes in 17%. Of the 434 episodes of cobalamin deficiency, 98.4% of serum methylmalonic acid levels and 95.9% of serum homocysteine levels were elevated (greater than 3 standard deviations above the mean in normal subjects). Only one patient had normal levels of both metabolites. Serum homocysteine levels were increased in 91% of the 123 episodes of folate deficiency. Methylmalonic acid was elevated in 12.2% of the folate-deficient patients; in all but one, the elevation was attributable to renal insufficiency or hypovolemia.
For the cobalamin-deficient patients, measuring serum metabolite concentrations proved to be a highly sensitive test of deficiency. We conclude that normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.
钴胺素（维生素B12）缺乏的患者通常缺乏严重巨幼细胞贫血的许多典型特征；由于血清钴胺素水平降低的诊断特异性较低，明确诊断这种缺乏症往往很困难。我们检测了测定血清甲基丙二酸和总同型半胱氨酸浓度对诊断明确的钴胺素缺乏患者的敏感性，并将结果与明确的叶酸缺乏患者的结果进行比较。
对1982年至1989年在两家大学医院就诊且符合钴胺素和叶酸缺乏状态标准的所有患者，以及1968年至1981年有储存血清的此类患者，检测其血清代谢产物。共有406例患者发生434次钴胺素缺乏发作，119例患者发生123次叶酸缺乏发作。缺乏状态的标准包括血清维生素水平、血液学和神经学检查结果以及对治疗的反应。97%的钴胺素缺乏患者和76%的叶酸缺乏患者记录了治疗反应。代谢产物水平采用改良技术，通过毛细管气相色谱法和质谱法进行测定。
大多数钴胺素缺乏患者患有潜在的恶性贫血；三分之二为黑人或拉丁裔。28%的患者血细胞比容正常，17%的患者平均细胞体积正常。在434次钴胺素缺乏发作中，98.4%的血清甲基丙二酸水平和95.9%的血清同型半胱氨酸水平升高（高于正常受试者平均值3个标准差以上）。只有1例患者两种代谢产物水平均正常。在123次叶酸缺乏发作中，91%的患者血清同型半胱氨酸水平升高。12.2%的叶酸缺乏患者甲基丙二酸升高；除1例患者外，所有患者的升高均归因于肾功能不全或血容量不足。
对于钴胺素缺乏患者，测定血清代谢产物浓度被证明是一种高度敏感的缺乏检测方法。我们得出结论，甲基丙二酸和总同型半胱氨酸水平均正常几乎可以肯定排除临床上显著的钴胺素缺乏。
