Cobalamin Malabsorption due to a Dysfunctional Intrinsic Factor

An 18-year-old French Canadian student presenting with a severe normocytic anemia, had undetectable serum cobalamin but normal gastric acidity and no evidence of generalized malabsorption. The gastric juice contained a normal quantity of intrinsic factor. Serum anti-intrinsic factor blocking antibodies were not present. Absorption of radiolabelled cobalamin given orally in the Schilling test was decreased but this was corrected by using hog intrinsic factor. Patient gastric juice bound cobalamin normally but did not promote uptake of this vitamin by homogenates of guinea pig intestinal mucosa. A family study showed normal cobalamin absorption for all tested subjects, as well as two α-hemoglobin gene deletions in the father and a single α-gene deletion in the patient. The cobalamin malabsorption is likely due to a defect of the patient's intrinsic factor at the ilea! receptor sire.