Decreased activity of intestinal and urinary intrinsic factor receptor in Gräsbeck-Imerslund disease [corrected].
OBJECTIVE
The pathogenesis of inherited intestinal cobalamin malabsorption (Gräsbeck-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.


METHODS
Intrinsic factor-cobalamin receptor activity was measured using radioisotope assay and gel-filtration exclusion chromatography in ileal biopsy specimens and urine concentrates from 4 patients with Gräsbeck-Imerslund disease and 5 controls.


RESULTS
Receptor activity was 164 +/- 13 fmol/mg of protein in control biopsy specimens and < 2.6 fmol/mg protein in specimens from patients. The association constant was estimated to be 3.8 +/- 0.4 (nmol/L)-1 in controls. A dramatic decrease in receptor activity was also observed in urine concentrate from patients with an association constant of 1.9 and 3.3 (nmol/L)-1. Isoelectrofocusing of the cross-linked intrinsic factor-cobalamin receptor complex showed an isoelectric point at 4.8 in a patient as well as in control samples.


CONCLUSIONS
It is concluded that Gräsbeck-Imerslund disease is related to decreased intrinsic factor-receptor activity in intestinal mucosa; the receptor assay in urine can be helpful for diagnosis.
Guéant
J L
JL
Laboratory of Cellular and Molecular Nutrition, INSERM Unité 308, Bordeaux, France.
Saunier
M
M
Gastin
I
I
Safi
A
A
Lamireau
T
T
Duclos
B
B
Bigard
M A
MA
Gräsbeck
R
R
D000328:Adult; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007082:Ileum / Q000737:chemistry*; D007223:Infant; D008286:Malabsorption Syndromes / Q000378:metabolism*; D008297:Male; D011956:Receptors, Cell Surface / Q000032:analysis*; D014805:Vitamin B 12 / Q000378:metabolism*
D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D014805:Vitamin B 12