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Intestinal Cobalamin Malabsorption (Discovered in the Beagle)

Intestinal Cobalamin Malabsorption (ICM) or Imerslund-Gräsbeck Syndrome is a metabolic disorder resulting from a failure to absorb vitamin B12 in the small intestine of the gut causing retarded growth, a low count of the oxygen carrying red blood cells (anemia), and a low count of white blood cells (immune system cells).

Found in

1 in 2,500 dogs

in our testing

Key Signs

Growth retardation, Anemia, Neutropenia, Loss of appetite

Age of Onset

0 to 2 yrs

Juvenile onset

Inheritance

Autosomal Recessive

For autosomal recessive disorders, dogs with two copies of the variant are at risk of developing the condition. Dogs with one copy of the variant are considered carriers and are usually not at risk of developing the disorder. However, carriers of some complex variants grouped in this category may be associated with a low risk of developing the disorder. Individuals with one or two copies may pass the disorder-associated variant to their puppies if bred.

Likelihood of the Condition

High likelihood

At risk dogs are highly likely to show signs of this disease in their lifetime.

What to Do

Here’s how to care for a dog with ICM

Partner with your veterinarian to make a plan regarding your dog’s well-being, including any insights provided through genetic testing. If your pet is at risk or is showing signs of this disorder, then the first step is to speak with your veterinarian.

For Veterinarians

Here’s what a vet needs to know about ICM

Initial signs of intestinal cobalamin malabsorption can be seen in puppies 6 to 12 weeks of age, when cobalamin store become depleted. Puppies with IGS suffer from weakness and loss of appetite and fail to grow normally Bloodwork shows anemia, neutropenia, and low cobalamin concentrations. High levels of homocysteine and methylmalonic acid can also be observed in the blood. Proteinuria is typically present.

Treatment consists of regular vitamin B12 supplementation; injection provides rapid absorption but oral vitamin B12 may also be used.

For Breeders

Planning to breed a dog with this genetic variant?

There are many responsibilities to consider when breeding dogs. Regardless of test results it is important that your dog is in good general health and that you are in a position to care for the puppies if new responsible owners are not found. For first time or novice breeders, advice can be found at most kennel club websites.

This disease is autosomal recessive meaning that two copies of the mutation are needed for disease signs to occur. A carrier dog with one copy of the ICM mutation can be safely bred with a clear dog with no copies of the ICM mutation. About half of the puppies will have one copy (carriers) and half will have no copies of the ICM mutation. A dog with two copies of the ICM mutation can be safely bred with a clear dog. The resulting puppies will all be carriers. Puppies in a litter which is expected to contain carriers should be tested prior to breeding. Carrier to carrier matings are not advised as the resulting litter may contain affected puppies. Please note: It is possible that disease signs similar to the ones caused by the ICM mutation could develop due to a different genetic or clinical cause.

Technical Details

Gene CUBN
Variant Deletion
Chromosome 2
Coordinate 19,796,293

All coordinates reference CanFam3.1

References & Credit

Credit to our scientific colleagues:

Drögemüller, M., Jagannathan, V., Howard, J., Bruggmann, R., Drögemüller, C., Ruetten, M., … Kook, P. H. (2014). A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption). Animal Genetics, 45(1), 148–150. View the article