Abstract
ABSTRACT: Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic atiduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Grasbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fyfe, J., Giger, U., Hall, C. et al. Inherited Selective Intestinal Cobalamin Malabsorption and Cobalamin Deficiency in Dogs. Pediatr Res 29, 24–31 (1991). https://doi.org/10.1203/00006450-199101000-00006
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199101000-00006
This article is cited by
-
Proteinuria and events beyond the slit
Pediatric Nephrology (2010)
-
Receptor-mediated endocytosis in renal proximal tubule
Pflügers Archiv - European Journal of Physiology (2009)
-
Gene expression analysis defines the proximal tubule as the compartment for endocytic receptor-mediated uptake in the Xenopus pronephric kidney
Pflügers Archiv - European Journal of Physiology (2008)
-
The Finnish disease heritage III: the individual diseases
Human Genetics (2003)
-
Megalin and cubilin: multifunctional endocytic receptors
Nature Reviews Molecular Cell Biology (2002)