Clinical Chemistry
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Clinical Chemistry 46: 1744-1750, 2000;
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(Clinical Chemistry. 2000;46:1744-1750.)
© 2000 American Association for Clinical Chemistry, Inc.

Articles

Evaluation of Indicators of Cobalamin Deficiency Defined as Cobalamin-induced Reduction in Increased Serum Methylmalonic Acid

Bjørn J. Bolann1,a, Jan Dag Solli2, Jörn Schneede5, Kjell A. Grøttum2, Arne Loraas2, Morgan Stokkeland2, Asbjørn Stallemo2, Arne Schjøth3, Rolf Bruun Bie4, Helga Refsum5 and Per Magne Ueland5

1 Laboratory of Clinical Biochemistry, Haukeland University Hospital, N-5021 Bergen, Norway.

2 Medical Department,

3 Department of Clinical Chemistry, and

4 Department of Pathology, N-4604 Kristiansand, Norway.

5 LOCUS for Homocysteine and Related Vitamins, Armauer Hansens hus, University of Bergen, N-5020 Bergen, Norway.
a Author for correspondence. Fax 47-5-5973115; e-mail bjorn.bolann{at}ikb.uib.no

Background: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state.

Methods: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17–87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 µmol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used.

Results: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0.810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information.

Conclusions: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.




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