A novel compound heterozygous GAA mutation in a Chinese family with juvenile onset form of Pompe disease with cardiomyopathy.

Pompe disease is an autosomal recessive disorder resulting from a deficiency of acid α-glucosidase (GAA). It is uncommon in the mainland of China, due to rare mutations in the GAA gene. The aim of this work was to elucidate the causative role of a novel compound heterozygous mutation of juvenile onset Pompe disease. In this study, clinical samples were obtained from two siblings with muscle weakness, recurrent airway infections, cardiomyopathy and respiratory insufficiency in a non-consanguineous Chinese family. The α-glucosidase activity in leukocytes of both children was low. Next-generation sequencing was performed on the 19 coding exons of GAA in both children, with confirmation by Sanger sequencing. Next-generation sequencing showed the same compound heterozygous GAA mutation (c.1216G>A p.Asp406Asn and c.1935C>A p.Asp645Glu) in both children. As this mutation is consistent with the clinical manifestations of juvenile onset Pompe disease and no other mutations were detected after scanning the gene sequence, we suggest that the Pompe disease phenotype is caused by compound heterozygosity for c.1216G>A and c.1935C>A. As c.1216G>A is not currently listed in the Pompe disease Mutation Database, this information about Pompe disease in a Chinese population is of particular interest.