Lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency that prevents the degradation of lysosomal glycogen and causes its accumulation in skeletal and cardiac muscle and other tissues. In the Lapphund breeds it produces a severe infantile form with progressive muscle weakness, cardiomegaly, megaoesophagus and lethal cardiorespiratory failure. It is inherited in an autosomal recessive manner and is associated with a GTG→stop mutation in the GAA gene.

Affected breeds: Finnish Lapphund (carrier frequency ~5%, 5/95) and Lapponian Herder (carriers ~2%, 2/99). The same variant was identified in a historical Swedish Lapphund (where the disease was originally described), but no carriers were detected in the current cohort of 34 Swedish Lapphunds. The mutation has not been detected in other breeds.

- Progressive muscle weakness and difficulty moving from puppyhood
- Cardiomegaly and cardiorespiratory failure
- Megaesophagus with regurgitation and vomiting
- Growth retardation and weight loss
- Glycogen accumulation in liver, muscle and heart
- Lethal course in the first months of life

Canine Pompe disease was described in the 1960s-80s in Swedish Lapphunds as a biochemical model of the human infantile form, with absent acid alpha-glucosidase activity. More than forty years later, Seppälä and colleagues (2013) identified the causal mutation: a c.2237G>A change in the GAA gene that generates a premature stop codon (p.W746*), truncating the last 206 amino acids of the protein. The same mutation was confirmed in one of the historical Swedish Lapphunds (born in 1979) and was also detected in the Lapponian Herder, which allowed a genetic test for the Scandinavian breeds to be developed.

- Test breeding animals with the GAA test (c.2237G>A) in the Lapphund breeds
- Do not mate two carriers: 25% risk of affected lethal homozygotes
- A carrier can be mated with a clear animal; offspring intended for breeding must be tested
- Prioritise screening in the Finnish Lapphund and the Lapponian Herder due to their carrier frequency
- Exclude affected animals from breeding

Differential diagnosis with other metabolic myopathies of the puppy (GSD Ia, GSD IIIa, congenital myopathies) and with causes of megaesophagus and cardiomegaly. Determination of acid alpha-glucosidase activity in muscle or leukocytes and the genetic test are confirmatory. Megaesophagus is a distinctive sign in the dog compared with humans, probably related to the quadrupedal posture.

1. Seppälä EH, Reuser AJJ, Lohi H (2013) A nonsense mutation in the acid alpha-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds. PLoS One 8(2):e56825. PMID: 23457621
2. OMIA:000419-9615. Glycogen storage disease II in Canis lupus familiaris. https://omia.org/OMIA000419/9615/