Intestinal cobalamin (vitamin B12) malabsorption, AMN related

(Imerslund-Grasbeck Syndrome, megaloblastic anemia)

 

Gene: AMN

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations: 

Giant Schnauzer mutation: Deletion, AMN gene; c.1113_1145 del. 33nt, p.(G372_A382 del), exon8

Australian Shepherd mutation: Substitution, AMN gene; c.3 G>A

Medical systems: Metabolic, blood, digestive

Breeds: Australian Shepherd, Schnauzer - Giant

Age of onset of symptoms: Between 2 and 4 years

The malabsorption of cobalamin (or vitamin B12) is a genetic disorder caused by a defect in an intestinal protein involved in the absorption of vitamin B12.  Vitamin B12 plays an important role in metabolism but cannot be synthesized by the animal and must absolutely be absorbed from the diet.  Cobalamin deficiency causes loss of appetite, stunted growth, lack of energy, anemia, and increased proteins and methylmalonic acid in the urine.  Occasionally there are behavior problems.  Dietary vitamin B12 supplementation may be a treatment option for this condition.

Cobalamin malabsorption in the dog can be cause by genetic defects in either of the Cubilin (CUBN) or the AMN genes, and for both genes, by more than one mutation.  The CUBN gene mutation tends to have a wider breed distribution than the AMN gene mutation.

 

References:

OMIA link: [0565-9615]

Kather S, Grützner N, Kook PH, et al. (2020) Review of cobalamin status and disorders of cobalamin metabolism in dogs. J Vet Intern Med. 34(1):13-28. [pubmed/31758868]

Kook PH, Hersberger M. (2019) Daily oral cyanocobalamin supplementation in Beagles with hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome) maintains normal clinical and cellular cobalamin status. J Vet Intern Med. 33(2):751-757. [pubmed/30554416]

Stanley E, Appleman E, Schlag A, Siegel A. (2019) Relationship between cobalamin and folate deficiencies and anemia in dogs. J Vet Intern Med. 2019 Jan;33(1):106-113. [pubmed/30499147]

Fyfe JC, Hemker SL, Frampton A, et al. (2018) Inherited selective cobalamin malabsorption in Komondor dogs associated with a CUBN splice site variant. BMC Vet Res 14:41. [pubmed/30591068]

Gold AJ, Scott MA, Fyfe JC. (2015) Failure to thrive and life-threatening complications due to inherited selective cobalamin malabsorption effectively managed in a juvenile Australian shepherd dog. Can Vet J. 56(10):1029-34. [pubmed/26483576]

He Q, Madsen M, Kildenney A, et al. (2005) Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo.  Blood 106(4)L1447-1453. [pubmed/15845892]