title: Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs.
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 aciduria 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-Gräsbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.
authors.affiliation: Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: J C
authors.initials: JC
authors.lastname: Fyfe
authors.forename: U
authors.initials: U
authors.lastname: Giger
authors.forename: C A
authors.initials: CA
authors.lastname: Hall
authors.forename: P F
authors.initials: PF
authors.lastname: Jezyk
authors.forename: S A
authors.initials: SA
authors.lastname: Klumpp
authors.forename: J S
authors.initials: JS
authors.lastname: Levine
authors.forename: D F
authors.initials: DF
authors.lastname: Patterson
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D005808:Genes, Recessive; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007437:Intrinsic Factor / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000172:deficiency; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*
chemical_list: D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D008764:Methylmalonic Acid; D007437:Intrinsic Factor; D014805:Vitamin B 12