Intestinal Cobalamin Malabsorption (Beagle Type)
Affected Genes: CUBN
Inheritance: Autosomal Recessive
Variant(canFam6):
chr2:16899385: 1 bp deletion C
Breed: Beagle
General Information: Intestinal cobalamin malabsorption (beagle type) is an inherited disorder in dogs that impairs the production of a protein essential for nutrient absorption, including the B vitamin cobalamin. After weaning, affected dogs show elevated levels of methylmalonic acid in their urine, indicating cobalamin deficiency, but symptoms such as anorexia, lethargy, poor weight gain, and degenerative liver disease may not be recognized for months or years. In severe cases, dogs can develop hepatic encephalopathy, leading to altered mental states, seizures, coma, and death. These dogs also exhibit increased urinary proteins and decreased blood cell synthesis, resulting in anemia and reduced neutrophils. Lifelong cobalamin supplementation is necessary, leading to disease remission in most cases within weeks, though increased urinary proteins persist.
How to Read Your Dog's Test Results for this Genetic Variant:
Two Variants Detected: Dog Likely Affected
One Variant Detected: Dog Unlikely Affected
No Variants Detected: No Effect
Gene / Testing Information: Genetic testing of the CUBN gene identifies if a dog is a carrier of intestinal cobalamin malabsorption (beagle type). This disorder is inherited in an autosomal recessive manner, requiring two copies of the mutated gene for a dog to develop the disease. Carrier dogs typically do not show symptoms but breeding two carriers increases the risk of affected puppies. Each pup from such a pairing has a 25% chance of having the disease and a 50% chance of being a carrier. To prevent affected pups, it is recommended not to breed known carriers together, ensuring that dogs without the mutation have no increased risk of producing affected offspring.
References:
Drogemuller M, Jagannathan V, Howard J, Bruggmann R, Drogemuller C, Ruetten M, Leeb T, Kook PH. A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund–Grasbeck syndrome (selective cobalamin malabsorption) Anim Genet. 2014 45(1):148-150.
Fyfe JC, Hemker SL, Venta PJ, Stebbing B, Giger U. Selective Intestinal Cobalamin Malabsorption with Proteinuria (Imerslund-Grasbeck Syndrome) in Juvenile Beagles. J Vet Intern Med. 2014 28(2):356-362.
Kook PH, Drogemuller M, Leeb T, Howard J, Ruetten M. Degenerative Liver Disease in Young Beagles with Hereditary Cobalamin Malabsorption Because of a Mutation in the Cubilin Gene. J Vet Intern Med. 2014 28(2):666-671.