Test Detail

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.

- 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/