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Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations
Author(s) -
Lindenbaum John,
Savage David G.,
Stabler Sally P.,
Allen Robert H.
Publication year - 1990
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830340205
Subject(s) - cobalamin , methylmalonic acid , homocysteine , medicine , megaloblastic anemia , vitamin b12 , gastroenterology , cyanocobalamin , endocrinology
Abstract 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.