Seven cases of Pompe disease from Greece

We present seven cases of Pompe disease (McKusick 232300; glycogen storage disease type II; acid maltase deficiency) from Greece. The onset of symptoms varied from early childhood to late adulthood, and the patients had quite variable duration of disease. All but one of them had muscle weakness and all had mildly to highly elevated serum creatine kinase. The diagnosis in all cases was confirmed by the finding of acid alpha-glucosidase (EC 3.2.1.3/20) deficiency in cultured skin fibroblasts. Thirteen mutant alleles were identified and nine different pathogenic mutations were encountered. Four were new: c.2071_2072insAGCCG leads to frameshift and total loss of function; c.1856G > A (p.Ser619Asn) leads to 90-95% loss of function; and the splice-site mutations c.1552-3C > G and c.2331+4A > G reduce the number of correct splicing events by more than 90%. The splice-site mutation c.-32-13T > G (IVS1-13T > G) was encountered four times and seems equally common among Greek and other caucasians. The other mutations: c.925G > A (p.Gly309Arg), c.[307T > G; 271G > A] (p.Cys103Gly; Asp91Asn), c.271del and c.1655T > C (p.Leu552Pro) have been reported earlier. Our study highlights the heterogeneity of Pompe disease in Greece and provides tools for diagnosis and carrier detection.