Glycogen Storage Disease Type IV (Norwegian Forest Cat)

 

Gene: GBE1

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.

Mutation: Insertion plus deletion, GBE1 gene; ins. 334bp, del. 6.2kb

Medical systems: Metabolic, muscular, neurologic

Breeds: Norwegian Forest Cat

Age of onset of symptoms: At birth or after a few months

Glycogen storage disease type IV is a genetic metabolic disease that is lethal and specific to Norwegian Forest Cats. This disease is caused by a defective enzyme called glycogen branching enzyme, which allows an accumulation of glycogen in nerve cells, muscle cells and liver cells and results in defective organ function.  Affected animals tend to die of hypoglycemia (low blood sugar levels), often at birth or several months after birth.  The animals that survive appear clinically normal until about 5 months of age whereupon neuromuscular degeneration becomes apparent.  These animals suffer from muscle atrophy and heart failure leading to death usually before 15 months of age.

 

References:

OMIA link: [0420-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Almodóvar-Payá A, Villarreal-Salazar M, de Luna N, et al. (2020) Preclinical research in glycogen storage diseases: A comprehensive review of current animal models. Int J Mol Sci 21:9621.  [pubmed/33348688]

Fyfe JC, Kurzhals RL, Hawkins MG, et al. (2007) A complex rearrangement in GBE1 causes both perinatal hypoglycemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats. Mol Genet Metab. 90(4):383-392. [pubmed/17257876]