Glycogen storage disease - GSD IV (Glycogen Branching Enzyme Deficiency)

Glycogen storage disease type IV (GSD IV) of the Norwegian forest cat is an inherited abnormality of glucose metabolism. Normally, excess glucose obtained in the diet or produced by conversion of proteins and fats is stored in many tissues as a very highly branched polymer (chain) of glucose residues called glycogen. A special biological catalyst called glycogen branching enzyme (GBE for short) is necessary during glycogen synthesis to produce the branching structure. When needed for energy, glucose molecules are removed from glycogen and digested within the tissue or released into the blood circulation for use by other tissues. The ability to add and remove glucose molecules from glycogen efficiently is dependent on its highly branched structure. Our studies have determined that GSD IV in Norwegian forest cats is due to an inherited deficiency of GBE. Affected kittens store a very abnormal glycogen, a glucose polymer devoid of branch points, in most tissues.

GSD IV is inherited as a simple autosomal recessive trait. Practically, this means that, though clinically-normal, both parents of an affected kitten are obligate carriers of the trait. The parents will pass their carrier status along to 50% of all their offspring, both male and female, when mated to a non-carrier cat. When two carriers are mated, 25% of the offspring will be affected and two-thirds of the clinically-normal littermates will be carriers. Because they are clinically-normal, carriers of GSD IV may be active breeders in a cattery, passing their carrier status along to the next generation, and never suspected until an affected kitten is born. Furthermore, because stillbirth or early death is not so uncommon for any of many reasons, a GSD IV affected kitten may be discarded without diagnosis and its carrier parents continue breeding unsuspected. One condition that can masquerade as neonatal death from GSD IV is neonatal isoerythrolysis (NI), a blood type-incompatibility problem that can cause death of newborn type A or type AB kittens born to type B queens a few hours to days after first nursing.

To overcome these problems there has been developed a definitive, DNA-based test. This test will allow Norwegian forest cat breeders to eliminate GSD IV carrier cats from their breeding programs while preserving desirable traits. The DNA test detects directly whether the mutation that causes GSD IV is present in a cat's DNA or not. When a cat is tested there are 3 possibilities:

The gen is present in two copies and the kitten will die before it reaches the age of 1 year old
The gen is present in one copy and the kitten is a carrier of the gen, but will not die from having just one copy
The gen is NOT present in the kitten (the kitten is genetically normal) and (of course) can't give the gene to an offspring nor die from it

Clinical Signs:

The disease caused by GBE deficiency in Norwegian forest cats is of two types. By far, the most common form is stillbirth or death within a few hours of birth. We believe this to be due to insufficient glucose available to produce energy during the birth process and the first hours of life. On rare occasions, an affected kitten will survive the neonatal period and appear normal until 5 months of age. Though less common, this is the more devastating form of the disease because by this age new owners are very attached to their kitten, and witness it go through months of neuromuscular degeneration. By eight months of age, GSD IV results in severe muscular weakness, atrophy and contractures, and inability to use the limbs. The cat may die suddenly from heart failure.

Affected Breeds:

Norwegian Forest Cat

Required Samples:

EDTA Blood, 1-2 mL or 2 buccal swabs

Price: $75 each (2008 niceau) further informationcan be obtained at: penngen@vet.upenn.edu in the US. There is also labs in Europe who can perform the test.