Alpha-glucosidase deficiency

From Dog

Canine α-glucosidase deficiency (Type II glycogenosis; juvenile Pompe disease) is a rare autosomal-recessive genetic lysosomal storage disease characterized by α-glucosidase deficiency as widespread organomegaly[1].

This disease affects only homozygous dogs, and heterozygous carriers are usually clinically normal. Primary breeds affected are the Finnish Lapphund and Lapponian Herder.

This canine disease is caused by a missense mutation in the GAA gene which is responsible for production of α-glucosidase that normally degrades α-1,4 and α -1,6 linkages in glycogen, maltose, and isomaltose[2]. As a consequence, the catalytically inactive alpha-glucosidase cannot convert glycogen, maltose and isomaltose into subunits and accumulates within cytosolic lysosomes, leading to cell death and eventual tissue destruction.

Over the course of months, a range of progressive clinical symptoms manifests due to muscle weakness[3].

Clinically affected dogs are usually under 2 years of age with a long history of anorexia, dysphagia, vomiting, progressive weakness, weight loss and heart murmurs[4].

Ultrasonography usually reveals esophageal dilatation characteristic of megaesophagus, hepatomegaly and cardiomegaly suggestive of hypertrophic cardiomyopathy. Blood tests typically show decreased ALP and elevated ALT, BUN and thrombocytosis.

Histological examination of biopsies usually reveals accumulation of glycogen-containing vacuoles in the cerebral cortex, liver, myocardium and oesophageal smooth muscle.

Diagnosis is usually based on biochemical testing of tissue samples for alpha-glucosidase activity, which is markedly reduced.

A differential diagnosis would include other genetic lysosomal storage diseases, as well as myasthenia gravis, centronuclear myopathy and nemaline myopathy.

Enzyme replacement therapy is currently the only effective treatment for human Pompe disease[5], but has not been trialled in canine patients, which invariable require euthanasia by two years of age.


  1. Walvoort HC et al (1985) Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease). J Inherit Metab Dis 8:38–46
  2. Montalvo AL et al (2006) Mutation profile of the GAA gene in 40 italian patients with late onset glycogen storage disease type II. Hum Mutat 27:999–1006
  3. Hirschhorn R & Reuser AJ (2001) Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Valle D, Sly WS, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill. pp:3389–3420
  4. Seppälä EH et al (2013) A Nonsense Mutation in the Acid α-Glucosidase Gene Causes Pompe Disease in Finnish and Swedish Lapphunds. PLoS One 8(2):e56825
  5. Sun B et al (2003) Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector. Mol Ther 7(4):467-477