Molecular diagnosis of German patients with late-onset glycogen storage disease type II

In patients with late-onset glycogen storage disease type II, one mutation, c. -32-13T>G, in the a-glucosidase (GAA) gene is identified frequently in European populations from different regions along with many rarer mutations. We have performed molecular genetic investigations in 18 German index patients with late-onset disease. The c. -j32-13T>G, c.525delT (p. Glu176fsX45), and c. 2481+ 102_2646+ 31del mutations were detected by PCR/restriction enzyme digest. Other mutations were detected by sequencing. All patients were compound heterozygous and 17 patients harboured the c. -32-13T> G mutation. Seven other previously described mutations (including the c. -32-13T> G) were identified, of which the p.C103G (c. 307T>G) and the c. 2481+ 102_2646+ 31del mutations were present each in three unrelated patients. Sequencing revealed five novel mutations. Conclusions: Genetic testing was able to identify the genetic defects in all patients and screening of the c. -32-13T>G mutation identified 94% of the cases. This is important for quick and reliable diagnosis, especially in view of enzyme replacement. Among the rarer mutations, c. 2481+102_2646+ 31del and p.C103G are rather frequent in Germany.