Genetic basis of Cobalamin malabsorption in Beagles - is caused by a mutation in the CUBN gene (c.786delC), resulting in a frameshift and premature stop codon, leading to non-functional cubilin protein. Cubilin forms part of the receptor complex (cubam) essential for absorption of vitamin B12 (cobalamin) from the intestinal tract and for reabsorption of certain proteins in the kidney. The disease is inherited as an autosomal recessive disorder, meaning affected dogs have two copies of the mutated gene; carriers are asymptomatic. This mutation causes Imerslund-Gräsbeck Syndrome (IGS) in Beagles, a condition characterized by selective intestinal malabsorption of cobalamin.
Pathophysiology - Failure to absorb cobalamin leads to cobalamin deficiency, resulting in metabolic disturbances such as methylmalonic aciduria and hyperammonemia. Affected dogs show hematologic abnormalities like anemia and neutropenia (low neutrophils). The kidney is involved with proteinuria due to loss of cubilin function. Clinically, dogs display signs of failure to thrive, lethargy, anorexia, poor weight gain, and in severe cases, neurological dysfunctions including hepatic encephalopathy. Degenerative liver disease similar to ovine white liver disease has been reported.
Complications - Failure to thrive and poor overall condition in young dogs. Anemia and immune dysfunction due to impaired blood cell production. Proteinuria reflecting kidney involvement. Progressive degenerative liver disease if untreated. Neurological signs such as altered mental status, seizures, and coma in advanced cases.
Why This Matters to Breeders and Vets - Breeders: Genetic testing is crucial to identify carriers and avoid breeding two carrier dogs, which could produce affected puppies. Vets: Early diagnosis and treatment with cobalamin supplementation can dramatically improve outcomes. Recognizing breed predisposition allows for timely intervention and genetic counseling.