Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease)

Abstract

Glycogen storage disease type II (Pompe disease: PD) is an autosomal recessively inherited fatal genetic disorder that results from the deficiency of a glycogen hydrolyzing enzyme, acid α-glucosidase encoded by the <i>GAA</i> gene. Here, we describe the molecular basis of genetic defects in an 8-month-old domestic short-haired cat with PD. The cat was previously diagnosed with PD based on the clinical and pathological findings of hypertrophic cardiomyopathy and excessive accumulation of glycogen in the cardiac muscles. Sanger sequencing was performed on 20 exons of the feline <i>GAA</i> gene using genomic DNA extracted from paraffin-embedded liver tissues. The affected cat was found to be homozygous for the <i>GAA</i>:c.1799G>A mutation resulting in an amino acid substitution (p.R600H) of acid α-glucosidase, a codon position of which is identical with three missense mutations (p.R600C, p.R600L, and p.R600H) causing human infantile-onset PD (IOPD). Several stability and pathogenicity predictors have also shown that the feline mutation is deleterious and severely decreases the stability of the GAA protein. The clinical, pathological, and molecular findings in the cat were similar to those of IOPD in humans. To our knowledge, this is the first report of a pathogenic mutation in a cat. Feline PD is an excellent model for human PD, especially IOPD.