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Overexpression of an unstable intrinsic factor-cobalamin receptor in Imerslund-Gräsbeck syndrome
D M Eaton1, J H Livingston, B Seetharam
1Division of Pediatrics and Child Health, University of Leeds, General Infirmary, England.
Abstract:
Two sisters with Imerslund-Gräsbeck syndrome who presented with clinical features of cobalamin deficiency are described. Intrinsic factor-cobalamin receptor (IFCR) activity and protein levels were determined in ileal biopsy specimens by using radioisotope assay and immunoblotting, respectively. IFCR activities in ileal homogenates expressed as femtomoles of ligand binding per milligram of protein were 38 +/- 4 in control tissue, 494 +/- 24 in patient 1, and 94 +/- 7 in patient 2. However, when assayed in the presence of IFCR antiserum, the ligand binding was inhibited by > 90% in both normal control and the patients with Imerslund-Gräsbeck syndrome. Immunoblotting of total membranes from the biopsy specimen of these 2 patients failed to detect an immunoreactive band of molecular mass of 185 kilodaltons. These findings are at variance with reports of decreased IFCR activity and indicate a new phenotype in which an active but an unstable receptor is overexpressed in Imerslund-Gräsbeck syndrome.
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