Lindenbaum J, Savage D G, Stabler S P, Allen R H
Department of Medicine, Columbia-Presbyterian Medical Center, New York 10032.
Am J Hematol. 1990 Jun;34(2):99-107. doi: 10.1002/ajh.2830340205.
The serum cobalamin level has been generally considered to be essentially 100% sensitive in the detection of the clinical disorders caused by cobalamin deficiency. We tested this hypothesis in two groups of patients. In patients with pernicious anemia or previous gastrectomy who received less than monthly maintenance therapy, early hematologic relapse was associated with elevation of the serum methylmalonic acid, total homocysteine, or both metabolites in 95% of instances, although the serum cobalamin was low in only 69%. In the absence of hematologic relapse, the methylmalonic acid was abnormal more than twice as frequently as the serum cobalamin. We also reviewed the records of 419 consecutive patients with recognized clinically significant cobalamin deficiency. Twelve patients were identified in whom deficiency was clearly present although the serum cobalamin was greater than 200 pg/ml. Anemia was usually absent or mild, but 5 had prominent neurological involvement that subsequently responded to cobalamin. Both the serum methylmalonic acid and total homocysteine were increased in each patient. The serum cobalamin was normal in 9 (5.2%) of 173 patients with recognized cobalamin deficiency seen in the last 5 years. Antibiotic treatment lowered the serum methylmalonic acid but not the total homocysteine level in two cobalamin-deficient patients, suggesting that propionic acid generated by the anaerobic gut flora may be a precursor of methylmalonic acid in deficient patients. We conclude that the serum cobalamin is normal in a significant minority of patients with cobalamin deficiency and that the measurement of serum metabolite concentrations facilitates the identification of such patients.
血清钴胺素水平通常被认为在检测由钴胺素缺乏引起的临床疾病方面具有近乎100%的敏感性。我们在两组患者中对这一假设进行了检验。在患有恶性贫血或既往接受胃切除术且维持治疗间隔时间少于每月一次的患者中，早期血液学复发与血清甲基丙二酸、总同型半胱氨酸或两者代谢产物升高相关，这种情况在95%的病例中出现，尽管血清钴胺素水平仅在69%的病例中降低。在无血液学复发的情况下，甲基丙二酸异常的频率是血清钴胺素的两倍多。我们还回顾了419例临床上已确诊的钴胺素缺乏患者的病历。其中12例患者虽血清钴胺素水平高于200 pg/ml，但钴胺素缺乏明确存在。这些患者通常无贫血或仅有轻度贫血，但5例有明显的神经受累，随后对钴胺素治疗有反应。每例患者的血清甲基丙二酸和总同型半胱氨酸均升高。在过去5年中确诊的173例钴胺素缺乏患者中，9例（5.2%）血清钴胺素正常。抗生素治疗使两名钴胺素缺乏患者的血清甲基丙二酸水平降低，但总同型半胱氨酸水平未降低，这表明厌氧肠道菌群产生的丙酸可能是缺乏患者甲基丙二酸的前体。我们得出结论，在相当一部分钴胺素缺乏患者中血清钴胺素水平正常，测定血清代谢物浓度有助于识别此类患者。
