In other species: domestic cat , cattle , sheep , Japanese quail

Possibly relevant human trait(s) and/or gene(s) (MIM number): 232300

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Also called Pompe disease, Pompe's disease, acid maltase deficiency, and generalised glycogenesis type II. A lysosomal storage disease in which there is a buildup (storage) of glycogen, due to the lack of the enzyme alpha-glucosidase, whose task is to break down glycogen into its constituent glucose molecules. Characterised by poor growth, incoordination, muscle weakness and eventual recumbency.

History: This canine disorder was first reported by Mostafa (1970), in a Swedish Lapland dog.

Molecular basis: Adopting the comparative candidate-gene approach (based on similarity of diagnostic signs with humans), Seppälä et al. (2013) sequenced the canine GAA gene (encoding acid α-glucosidase) in "two affected Finnish Lapphunds, their dam and an unrelated healthy 8-year-old Finnish Lapphund as control", revealing a causal nonsense mutation: a "c.2237G>A mutation leading to a premature stop codon at amino acid position 746", i.e. p.W746*. Using a cell line established decades ago from tongue tissue, the authors "were able to establish that one of the originally described Swedish Lapphunds with Pompe disease (born in 1979) was also homozygous for the same c.2237G>A mutation". Exactly the same mutation in the human GAA gene causes the same disease (see the MIM entry above).

Prevalence: Seppälä et al. (2013) "screened 95 Finnish Lapphunds, 99 Lapponian Herders and 34 Swedish Lapphunds" for the c.2237G>A; p.W746* causal mutation, observing 5%, 2% and zero carriers, respectively. This mutation was not present in 304 dogs from 21 other breeds.

Breeds: Finnish Lapphund, Swedish Lapphund.

Associated gene: