Imerslund-Grasbeck Syndrome (IGS) or intestinal malabsorption of cobalamin in Komondor

Vitamin B12 (cobalamin) is a member of the group of water-soluble B vitamins. Higher organisms cannot synthesize vitamin B12 on their own and rely on dietary intake or synthesis by symbiotic microorganisms. Humans obtain cobalamin exclusively from animal food. Vitamin B12 is essential for cell proliferation and is particularly important for the functioning of the nervous system and proper blood formation, although its deficiency affects most organs with cell renewal.

Intestinal malabsorption of cobalamin is a metabolic disorder that has been described in both humans and animals. In dogs, clinical signs of cobalamin malabsorption begin to appear around 6 to 12 weeks of age and include failure to thrive and chronic inappetence. Affected animals may exhibit neutropenia, non-regenerative anaemia, anisocytosis and poikilocytosis, megaloblastic changes of the bone marrow, decreased cobalamin levels, methylmalonic aciduria and homocysteinemia.

In Komondors, this phenotype is caused by the c.8746+1G>A mutation in the CUBN gene, whose protein is a part of a transmembrane complex important for the utilization of cobalamin from the intestine.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Fyfe, J.C., Hemker, S.L., Frampton, A., Raj, K., Nagy, P.L., Gibbon, K.J., Giger, U. : Inherited selective cobalamin malabsorption in Komondor dogs associated with a CUBN splice site variant. BMC Vet Res 14:418, 2018. Pubmed reference: 30591068