Glycogen Storage Disease Type Ia, GSD1a

 

Gene: G6PC

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Maltese mutation: Substitution, G6PC gene; c.363 G>C, p.(M121I), exon3

German Pinscher mutation: Insertion, G6PC gene; c.634_635 ins.76 nt

Medical system: Metabolic disorder

Breed: German Pinscher, Maltese Terrier, Yorkshire Terrier

Age of onset of symptoms: During gestation

Glycogen Storage Disease Type 1a is a metabolic disease involving a deficiency of the enzyme glucose-6-phosphatase such that glycogen cannot be broken down to glucose for energy.  This results in reduced energy available for cell metabolism and an accumulation of glycogen molecules in cells particularly within the heart, liver and kidneys.  This disease often leads to death of the fetus or newborn, resulting in unusually small and stillborn puppies.  Puppies that survive will show stunted growth, hypoglycemia, hepatomegaly, weakness and difficulty breathing, and will usually die before 6 months of age.

 

References:

OMIA link: [0418-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Christen M, Reineking W, Beineke A, et al. (2021) Polyadenine insertion disrupting the G6PC1 gene in German Pinschers with glycogen storage disease type Ia (GSD1A). Anim Genet 52:900-902.  [pubmed/34610166]

Kishnani PS, Faulkner E, VanCamp S, et al. (2001) Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia). Vet Pathol. 38(1):83-91. [pubmed/11199168]

Kishnani PS, Bao Y, Wu JY, et al. (1997) Isolation and nucleotide sequence of canine Glucose-6-phosphatase mRNA: Identification of mutation in puppies with Glycogen Storage Disease Type Ia.  Biochem Molecular Medicine 61:168-177. [pubmed/9259982]