Glycogen storage disease type IV (GSD IV) in Norwegian forest cats

The glycogen storage diseases (GSDs) are a group of autosomal recessive disorders of glycogen metabolism that result in glycogen accumulation in various tissues. The GSDs are categorized according to the deficient enzyme activity and have been numbered in the chronological order. Clinical symptoms of GSDs are different, depending on which enzyme is defected and the type and site of glycogen accumulation.

Glycogen storage disease type IV is caused by deficiency of α-1,4-glucan: α-1,4-glucan 6-glucosyl transferase (GBE = glycogen branching enzyme).

GSD IV appears in humans, horses and Norwegian forest cats as a hereditaly autosomal recesive disease .

In humans, GSD IV is also known as Andersen Disease. It is quite serious disorder. Patients usually die before 4 years of age for serious liver demages. Concentration of glycogen in livers is normal but glycogen is in abnormal structure - long linear chains instead of normal branched glycogen. Linear glycogen is insoluble. Accumulation of abnormal glycogen leads to liver enlargement and finally to liver failure. Clinical symptoms in humans are heterogenous.

In horses, GSD IV is caused by GBE1 nonsense mutation (p.Y34X) in GBE1 gene. Affected individuals surviving from 1 to 18 weeks and they die for hypoglycemic or cardiac abnormalities.

GSD IV in Norwegian forest cats is caused by different mutation than GBE1 mutation in humans or horses. Reason for the disorder is complex rearrangement of genomic DNA in GBE1 gene, constituted by a 334 bp insertion at the site of a 6.2 kb deletion that extends from intron 11 to intron 12. Abnormal glycogen is accumulated in myocytes, hepatocytes or neurons; that cause lethal tissue demages. Affected kittens die for hypoglycemia very early after birth. Surviving individuals die before 5 month of age for progressive muscular degeneration.

GCD IV is an autosomal recessive disorder. The disease affects cats with P/P (positive / positive) genotype only. Cats with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

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References:

John C. Fyfe, Rebeccah L. Kurzhals, Michelle G. Hawkins, Ping Wang, Naoya Yuhki, Urs Giger, Thomas J. Van Winkle, Mark E. Haskins, Donald F. Patterson, Paula S. Henthorn: 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, Molecular Genetics and Metabolism 90 (2007) 383-392