Test Detail

Imerslund-Gräsbeck Syndrome (IGS) Border Collie is a disorder of selective cobalamin (vitamin B12) malabsorption caused by a deficiency in the protein cubamolin, which is necessary for intestinal absorption of vitamin B12.\n\nCobalamin deficiency produces megaloblastic anaemia, progressive neurological deterioration, weight loss and weakness. Without lifelong treatment with vitamin B12 supplementation, the disease is lethal in the first months of life.

Border Collie: approximately 6% of carriers in a European series (Owczarek-Lipska et al.) and allele frequency 0.015 in 500 Border Collies from Japan. New Zealand Heading Dog: limited data (anecdotal cases, no verified published frequency).

- Progressive lethargy\n- Weight loss despite good appetite\n- Chronic diarrhoea\n- Megaloblastic anaemia (giant cells in blood)\n- Muscle weakness\n- Neurological deterioration (tremors, ataxia, seizures in advanced cases)\n- Dull, lustreless coat\n- Retarded growth in puppies

IGS was first described in humans in 1959 by Imerslund and Gräsbeck independently. In dogs, it was identified in Border Collies in Australia in 2006.\n\nThe causative mutation was mapped to chromosome 27 in the AMN (amnionless) gene, which encodes a transmembrane protein necessary for the internalisation of the cubamolin-vitamin B12 complex in the cells of the ileum.

- The syndrome is autosomal recessive: only homozygotes are affected; heterozygotes are carriers.\n- Do not mate two carriers together (25% risk of affected animals).\n- A carrier can be mated to a clear animal; test the offspring intended for breeding.\n- An affected animal treated with cobalamin may survive to breeding age: do not breed it anyway (it transmits the allele).\n- In puppies with anaemia and proteinuria, include IGS in the differential diagnosis.

Diagnosis is suspected from megaloblastic anaemia + serum cobalamin deficiency. Genetic testing confirms it.\n\nTreatment is lifelong: subcutaneous or intramuscular vitamin B12 injections (cyanocobalamin or hydroxocobalamin) every 1-2 weeks, then monthly. With treatment, affected dogs can have a relatively normal life.\n\nWithout treatment, the disease is lethal in the first 6-12 months of life.\n\nThe differential diagnosis includes: inflammatory bowel disease, early ageing, and other causes of anaemia.

1. Fyfe JC et al. 2013, mutación con cambio de marco en el exón 53 de CUBN que abole la función de cubam y causa el síndrome de Imerslund-Gräsbeck (PMID 23746554)
2. Malabsorción intestinal selectiva de cobalamina con proteinuria (Imerslund-Gräsbeck) en perros jóvenes (PMID 24433284)
3. OMIA:001786 Síndrome de Imerslund-Gräsbeck (CUBN)