The glycogen storage disease, a metabolic disease

The glycogen storage disease type IV (GSD IV) is an inherited disorder of glucose metabolism. In Norwegian Forest Cat, GSD IV is due to an inherited deficiency of an enzyme of glycogen synthesis called GBE (Glycogen Branching Enzyme). In affected cats, an abnormal form of glycogen (a polymer of glucose) is stored in most tissues.

Glycogen is the storage form of readily available glucose in animals. The glycogen storage disorders (GSD) are metabolic disorders that typically result in tissue accumulation of excessive or abnormally structured glycogen. These often cause liver and muscle disease and may or may not cause neuronal degeneration, hypoglycemia, and/or heart failure. GSD type IV is an autosomal recessive disorder of Norwegian forest cats previously defined in the United States (Fyfe JC et al ., 1992) that causes degeneration of neurons and cardiac and skeletal muscle with death ensuing before a year of age. Hypoglycemia in the immediate postnatal period often causes weakness and death unless treated. The disorder is due to a mutation of the glycogen branching enzyme gene (Fyfe JC et al ., 2007) and storage of abnormally structured glycogen (long outer chains).

Most affected kittens die at birth or soon after birth because they are not able to produce enough glucose during the birth process and the first hours of life. Rarely, affected kittens could live normally until 5 months of age, but the disease leads quickly to neuromuscular degeneration, to severe muscular atrophies, to cardiac failures and to death before 15 months of age.

Read more about NFO Olympia Edle von Rada's clinical course.

The GSD IV is inherited as an autosomal recessive trait in the Norwegian Forest Cat.
The GSD4 test detects directly the causative mutation in the GBE1 gene.
Statistics (frequency of carriers):
USA : 15%
Europe : 12%

The glycogen storage disease, an inherited disorder
The GSD IV is inherited as an autosomal recessive trait in the Norwegian Forest Cat. The DNA test supplies an answer among three possible situations:

test result
The cat is
Will develop
the disease?
Will transmit the genetic anomaly?
Normal homozygous
2 normal
copies of GBE1 gene
1 normal copy
and 1 defective copy of GBE1 gene
statistically to 50%
of its progeny
Mutated homozygous
2 defective
copies of GBE1 gene
neonatal mortality,
potential survival
until 15 months
Not able
to reproduce

Using this DNA test, breeders are able to detect very early carriers cats, to select breeding animals and to adapt breeding strategies in order to reduce neonatal mortality due to GSD IV, to avoid producing affected kittens, to avoid spreading the genetic defect in their lines or in the breed.

Associate Professor John C. Fyfe D.V.M. 1984
Washington-Oregon-Idaho Regional Program in Veterinary Medicine
Ph.D. 1994, University of Pennsylvania

Address: Laboratory of Comparative Medical Genetics 2209
Biomedical Physical Sciences Michigan State University East Lansing,
MI 48824
(517) 884-5348