DECREASED ACTIVITY OF INTESTINAL AND URINARY INTRINSIC-FACTOR IN GRASBECK-IMERSLUND DISEASE

Background/Aims: The pathogenesis of inherited intestinal cobalamin ma labsorption (Grasbeck-Imerslund disease) remains unknown. The authors studied whether the disease corresponds to a defective expression and/ or function of the intrinsic factor-cobalamin receptor in the ileum. M ethods: Intrinsic factor-cobalamin receptor activity was measured usin g radioisotope assay and gel-filtration exclusion chromatography in il eal biopsy specimens and urine concentrates from 4 patients with Grasb eck-Imerslund disease and 5 controls. Results: Receptor activity was 1 64 +/- 13 fmol/ mg of protein in control biopsy specimens and <2.6 fmo l/mg protein in specimens from patients. The association constant was estimated to be 3.8 +/- 0.4 (nmol/ L)(-1) in controls. A dramatic decr ease in receptor activity was also observed in urine concentrate from patients with an association constant of 1.9 and 3.3 (nmol/L)(-1). Iso electrofocusing of the cross-linked intrinsic factor-cobalamin recepto r complex showed an isoelectric point at 4.8 in a patient as well as i n control samples. Conclusions: It is concluded that Grasbeck-Imerslun d disease is related to decreased intrinsic factor-receptor activity i n intestinal mucosa; the receptor assay in urine can be helpful for di agnosis.