Type IV Glycogenosis

GSD IV (glycogen storage disease type IV) is part of a group of diseases, called glycogenoses. Type IV affects the Norwegian Forest Cat. They are well described pathologies also in humans, classified as rare diseases.
In a normal organism, the excess glucose obtained from the diet or from the conversion of proteins and fats is stored in a branched chain of polymers, glycogen, built using the enzyme GBE (glycogen branching enzyme) as a catalyst. When the body needs energy, glucose molecules are removed from the glycogen and released into the bloodstream or used by the tissues. The ability to efficiently add and remove glucose from glycogen depends on the complexity of its branching structure.
GSD IV is a  hereditary deficiency of the GBE enzyme: affected subjects store an abnormal form of glycogen which, therefore, leads to an insufficient use of glucose. Hence GSD IV can be considered a chronic hypoglycemia that inexorably worsens towards death (because the body is unable to use glucose effectively).
In cats, affected kittens die a few hours or days after birth, most likely because they do not have enough glucose to survive delivery and the first hours / days of life. The late form is rarer, for which the puppy is healthy up to 5/7 months and then suddenly shows a stunted growth and widespread weakness, with the following symptoms:

• high hyperthermia (over 40 °), insensitive to corticosteroids

• intermittent and generalized tremors that become permanent

• intermittent, "hiccup" weakness

• muscle weakness, followed by muscle atrophy, fibrotic contractures of

• joints that lead to movement and feeding difficulties and that require continuous assistance from the owner

• quadriplegia

Affected cats can survive up to 10/14 months. They die of cardiac arrest, sometimes after coma.
The disease is fatal and there is no cure.
It is possible that it is confused with neonatal isoerythrolysis  because the symptoms can suggest both pathologies. The only thing that can be done is the test (genetic for GSD IV, blood group identification with B allele typing for neonatal isoerythrolysis).

Genetic profile

The GDS IV mutation is recessive, which implies that the possibility of it expressing itself in the offspring exists only if both parents are carriers of the mutation.
There are 3 different possibilities:

• both parents are healthy (they are homozygous for the normal allele): the children are healthy and will not carry the mutation.

• if one of the parents is carrier (heterozygous) we will have about 50% carrier and 50% healthy cats among their offspring.

• When two carriers are mated we get 25% sick cats, 50% carriers and 25% healthy cats.

Recall that a carrier cat is a cat that does not have the disease and that will never develop it. However, he will be able to  to transmit the mutation to his children.

The test

A genetic test, on blood or buccal swab, is available to identify not only affected cats but also carriers.
Some laboratories that perform this test are:

Vetogenic
Genefast
Antagen
Genindexe
Laboklin
PennGen

Each laboratory provides for the sending home, upon request, of the test material (swabs or blood collection tubes), together with the necessary documentation. In some cases it is required, for a correct identification of the cat, that the microchip is applied.

Insights

• FYFE et al. (2007) A complex rearrangement in GBE1 causes both perinatal hypoglycaemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats, Mol Genet Metab. 90, 4, 383-92.

• http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17257876

• Glycogenoses on Wikipedia

• FYFE et al. (1992) Glycogen storage disease type IV: inherited deficiency of branching enzyme activity in cats., Pediatr Res. 32, 6, 719-25.FYFE (1995)

• Glycogen storage disease in cats, J Am Vet Med Assoc. 206, 3, 286.

• GASCHEN et al. In Congenital feline myopathies, Glycogen Storage disease type IV, 360-361

• http://www.winterfyre.com/testing/

• http://gsd4.de.vu/ v

• Text taken da  http: //www.clubnorvegesi.com/