Atypical cobalamin deficiency. Subtle biochemical evidence of deficiency is commonly demonstrable in patients without megaloblastic anemia and is often associated with protein-bound cobalamin malabsorption

J Lab Clin Med. 1987 Apr;109(4):454-63.


We performed studies in 25 patients with low serum cobalamin levels who had few if any clinical or hematologic findings of cobalamin deficiency. All but three had morphologically normoblastic hematopoiesis, and 15 were not even anemic. None of those tested excreted methylmalonic acid or homocystine. Nevertheless, the dUST identified metabolic abnormalities in 18 of the 25 cases. In vitro additives were essential in the dUST. Especially noteworthy was MTHF, whose addition unmasked an otherwise undetectable dUST abnormality in four cases. Why MTHF appears to act as a "stress test" in this setting is unknown but deserves further attention. Seven patients had early forms of classical malabsorptive states such as pernicious anemia, defined by abnormal Schilling test results. Among the rest, seven of 13 patients displayed malabsorption of protein-bound cobalamin despite normal absorption of free cobalamin by the Schilling test. In two patients, initially normal Schilling test results became abnormal the following year. These findings demonstrate that seemingly falsely low serum cobalamin levels often indicate subtle biochemical cobalamin deficiency. Early stages of pernicious anemia or other classical malabsorptive states are sometimes responsible for such subtle deficiency. However, malabsorption confined to protein-bound cobalamin is an equally common cause. Current concepts of cobalamin deficiency and the absorptive defects that can cause it should be expanded to include atypical defects requiring newer methods of identification.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / pathology
  • Deoxyuridine
  • Female
  • Folic Acid Deficiency / blood
  • Humans
  • In Vitro Techniques
  • Intestinal Absorption*
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Binding
  • Tetrahydrofolates / pharmacology
  • Vitamin B 12 / metabolism*
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / drug therapy
  • Vitamin B 12 Deficiency / metabolism*


  • Tetrahydrofolates
  • Vitamin B 12
  • 5-methyltetrahydrofolate
  • Deoxyuridine