Two extremes of the clinical spectrum of glycogen storage disease type II in one family: a matter of genotype.

Mutation analysis was performed in a nonconsanguineous Dutch caucasian family with a grandfather presenting the first symptoms of glycogen storage disease type II (acid alpha-glucosidase deficiency) in the sixth decade of life and a grandchild with onset of symptoms shortly after birth. The grandfather was identified as compound heterozygote having the IVS1(-13T-->G)/delta T525 combination of mutant acid alpha-glucosidase alleles, the affected third generation offspring as homozygote delta T525/delta T525. The disease phenotypes in this family are in accordance with the genotypes since the IVS1(-13T-->G) mutation reduces acid alpha-glucosidase synthesis by 60 to 80%, whereas the delta T525 mutation completely prohibits the formation of catalytically active enzyme. Four additional families were identified with patients homozygote for delta T525 and five others with an equally deleterious delta T525/delta exon 18 genotype. The nine latter patients had typically the infantile form of glycogen storage disease type II. The genotype-phenotype correlation is irrefutable.