Test Detail

Glycogen storage disease type IV (glycogen branching enzyme deficiency) of the Norwegian Forest Cat, a hereditary and lethal storage disease. The enzyme deficiency causes accumulation of abnormal glycogen (polyglucosans) in muscle, the nervous system and other tissues. It may present as perinatal death or as progressive neuromuscular disease in young cats. There is no treatment and control is based on avoiding matings between carriers.

Currently a rare disease thanks to breeding control. Historically relevant in Norwegian Forest Cat lines in Scandinavia and North America. Current carrier frequencies are not well quantified (limited data).

- Stillbirths or neonatal death in the first hours or days
- In juvenile forms (around 5-8 months): generalised weakness and muscle atrophy
- Muscle tremors and recurrent fever
- Anorexia and general deterioration
- Difficulty walking, jumping or maintaining posture
- Seizures in advanced stages
- Death or euthanasia due to poor prognosis

The disease was recognised in the Norwegian Forest Cat in the early 1990s, with descriptions of kittens stillborn and of young cats with progressive muscle weakness in the United States. Clinical and pathological studies established that it was a type IV glycogenosis with autosomal recessive inheritance. Subsequent work identified mutations in the GBE1 gene responsible for the condition. The availability of the DNA test allowed breeders of the breed to reduce the disease substantially in recent decades.

- Test Norwegian Forest Cat breeding cats before the first mating
- Never mate carrier with carrier: 25% risk of affected kittens
- A carrier may be mated to a clear cat, and only clear offspring kept if the aim is to eliminate the allele
- Unexplained death of entire litters at birth in the breed should prompt investigation and testing of the parents
- Report the results to the breed club to keep the register up to date

The differential diagnosis includes other feline storage diseases, inflammatory myopathies and infectious causes of stillbirth (panleukopenia, toxoplasmosis). Confirmation relies on branching enzyme activity in leukocytes or tissues and on the observation of polyglucosans in biopsies. The DNA test is conclusive for carrier status and the basis of genetic counselling.

1. Fyfe JC, Kurzhals RL, Hawkins MG, Wang P, Yuhki N, Giger U, Van Winkle TJ, Haskins ME, Patterson DF. 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) (PMID 17257876).
2. OMIA:000420-9685 (Glycogen storage disease IV, GBE1, Felis catus).