Glycogen Storage Disease Type IV

Glycogen storage disease type IV in cats is characterized by a deficiency in the glycogen branching enzyme encoded by the GBE1 gene. Clinically, affected cats present with cardiac and neuromuscular problems, provided they manage to survive the postnatal period.

Symptoms

Affected cats usually die shortly after birth due to hypoglycemia. Those who survive experience a rapid progression of clinical symptoms beginning around 5 months of age. These include neuromuscular and cardiac problems that may progress to tetraparesis, severe muscle atrophy, cardiac conduction defects and cardiomyocyte degeneration.

Disease Management

Currently, there is no specific treatment for this disease in cats.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Glycogen storage disease type IV is caused by a deficiency in the glycogen branching enzyme encoded by the GBE1 gene, which affects glycogen synthesis and degradation and leads to the accumulation of an abnormal amylopectin-like polyglucan in various tissues. The variant described in the GBE1 gene consists of a complex DNA rearrangement, with an insertion at the site of a deletion that results in the deletion of exon 12.

Most affected breeds

Norwegian Forest

Bibliography

Fyfe JC, Kurzhals RL, Hawkins MG, et al. 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. 2007 Apr