Glycogen storage disease Ia (GSD Ia) in Maltese

Glycogenosis Ia (GSD Ia, Glycogen Storage Disease) is a severe disorder of glycogen metabolism characterized by accumulation of glycogen, especially in the liver. Symptoms include severe liver enlargement, general failure to thrive, lethargy, coma, and death.

The disease in the Maltese is caused by a c.363G>C missense mutation in the G6PC gene, encoding the enzyme glucose-6-phosphatase, which catalyses the conversion of glucose-6-phosphate to glucose. The mutant G6PC has 15-fold lower activity, leading to severe hypoglycemia and glycogen storage and progressive hepatomegaly.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Kishnani, P.S., Bao, Y., Wu, J.Y., Brix, A.E., Lin, J.L., Chen, Y.T. : Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA: identification of mutation in puppies with glycogen storage disease type Ia. Biochem Mol Med 61:168-77, 1997. Pubmed reference: 9259982.