A case of childhood Pompe disease demonstrating phenotypic variability of p.Asp645Asn

Neuromuscul Disord. 2004 Jun;14(6):371-4. doi: 10.1016/j.nmd.2004.02.012.


A six-year-old child presented at 8 months of age with proximal muscle weakness and mild cardiac hypertrophy. Some alpha-glucosidase activity was detected in muscle but not in fibroblasts. As none of the two pathogenic mutations, [c.1933G>A]+[c.2702T>A] (Asp645Asn/Leu901Gln), led to detectable alpha-glucosidase activity upon expression in COS cells, the phenotype of the patient remained unexplained. A functionally comparable set of mutations, Asp645Asn/insGnt2243, was reported previously to cause classic infantile Pompe disease [Biochem Biophys Res Commun 244 (1998) 921]. We conclude that secondary genetic or environmental factors can be decisive for the phenotypic outcome of classic infantile versus childhood Pompe disease, when the acid alpha-glucosidase activity is extremely low.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Asparagine / genetics
  • Aspartic Acid / genetics
  • Blotting, Western / methods
  • COS Cells
  • Chlorocebus aethiops
  • DNA Mutational Analysis
  • Echocardiography, Three-Dimensional / methods
  • Fibroblasts / metabolism
  • Glycogen Storage Disease Type II / genetics*
  • Glycogen Storage Disease Type II / metabolism
  • Humans
  • Infant
  • Male
  • Muscles / metabolism
  • Mutation*
  • Phenotype*
  • Transfection / methods
  • alpha-Glucosidases / genetics*
  • alpha-Glucosidases / metabolism


  • Aspartic Acid
  • Asparagine
  • alpha-Glucosidases