Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)

Abstract

The pathology of canine glycogen storage disease type II (acid alpha-glucosidase deficiency, GSD II) was studied in three genetically related Lapland dogs and compared to the pathology of human GSD II (McKusick 23230). Canine GSD II closely parallels the infantile form of the human disease, except for the presence of oesophageal dilatation. Generalized glycogen storage particularly affected muscular tissues (skeletal, oesophageal, cardiac and smooth muscle). The altered cells showed glycogen accumulation in the cytosol and in autophagic membrane-bound vacuoles (glycogenosomes). They also showed increased acid phosphatase activity consistent with the lysosomal nature of this storage disorder. The cytopathology in canine and human GSD II appears to evolve from segregation of glycogen during regular cellular autophagy, phagolysosomal accumulation of the undigested glycogen, and eventually rupture of distended glycogenosomes. This study indicates that the usefulness of canine GSD II as an animal model of human disease, extends to the area of pathogenesis.

Temporal Neuropathologic and Behavioral Phenotype of 6neo/6neoPompe Disease Mice

“…Several papers describe Pompe-like phenotypes in each of three additional species: spontaneously mutant Shorthorn and Brahman cattle (43), Lapland dogs (44), and Japanese quail (45). For experimental therapeutic studies, however, cattle are too large to test with expensive therapeutic agents, and dogs appear to be unavailable in sufficient quantity, though they do show extensive glycogen deposition and granulovesicular abnormalities in cells of the CNS.…”

Glycogen storage disease type II in the Lapland dog

“…Later a family of Lapland dogs was traced in which the disease appeared (7). Confirmation of the metabolic defect (acid a-glucosidase deficiency) was obtained in biochemical studies with heart, skeletal muscle, liver, and cultured tongue fibroblasts of an affected dog (8) (11). In routine histopathology, heavy and optically empty vacuolation was observed in the muscle fibres.…”

A Nonsense Mutation in the Acid α-Glucosidase Gene Causes Pompe Disease in Finnish and Swedish Lapphunds

“…The clinical, pathological and biochemical characteristics of classic infantile Pompe disease in humans and dogs resemble each other very well [6]–[8]. The pathogenesis in both species implies the total absence of acid α-glucosidase activity, generalized glycogen storage leading to progressive muscular weakness, cardiac hypertrophy, cardio-respiratory failure and death.…”

“…Clinical signs and symptoms of the affected dogs included oesophageal dilation induced vomiting, progressive muscular weakness, loss of condition, clinical heart disease, and myocardial hypertrophy, the severity of which required euthanasia at about 1.5 years of age [3], [4], [6], [7]. Pathological findings revealed accumulation of glycogen containing vacuoles in cerebral cortex, liver, and myocardial plus oesophageal smooth muscle, and ultrastructural evidence of a lysosomal glycogen storage disorder [8]. Biochemical studies demonstrated a severe deficiency of acid α-glucosidase activity in heart, skeletal muscle and liver [9].…”