A six-year-old child presented at 8 months of age with proximal muscle weakness and mild cardiac hypertrophy. Some α-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 α-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 α-glucosidase activity is extremely low.

α-Glucosidase, Acid maltase, Glycogen storage disease, Mutation analysis, Pompe disease
dx.doi.org/10.1016/j.nmd.2004.02.012, hdl.handle.net/1765/66134
Neuromuscular Disorders
Department of Clinical Genetics

Kroos, M.A, Kirschner, J, Gellerich, F.N, Hermans, M.M.P, van der Ploeg, A.T, Reuser, A.J.J, & Korinthenberg, R. (2004). A case of childhood Pompe disease demonstrating phenotypic variability of p.Asp645Asn. Neuromuscular Disorders, 14(6), 371–374. doi:10.1016/j.nmd.2004.02.012