Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Background:Pompe disease or glycogenosis type II is an autosomal recessive disorder of glycogen metabolism caused by the deficiency of lysosomal Alpha glucosidase enzyme (GAA) due to mutations of the Alpha glucosidase gene (GAA) which results in lysosomal and cytoplasmic accumulations of glycogen eventually leading to tissue destruction especially the cardiac and skeletal muscles. Aim of the Work:The aim of this study was to screen cases of Pompe disease among highly suspected Egyptian pediatric patients referred to Cairo University Children{u2019}s Hospital (Abul-Rish), to identify the presence of Acid alpha glucosidase (GAA) gene mutations and shed light on the importance of molecular analysis of this potentially fatal disease. Methods:13 unrelated pediatric patients were included. Confirmation of clinically suspected Pompe disease was initially performed through measurement of the GAA enzyme level using fluorometric technique then molecular analysis using Sanger sequencing methodof GAA gene was carried out. Results:Genetic diagnosis of 11/13 (84.6%) of the studied cohort was accomplished through detecting the culprit disease causing variant in homozygous pattern in their GAA gene. 10/11 (90.9%) of these variants were missense, while 1/11 (9.1%) was a splice site (null) variant c.956-1G>C. According to ACMG guidelines and standards; 10/11 (90.9%) of those variants were classified as pathogenic, while 1/11 (9.1%) c.1979G>A (p.Arg660His)was classified as likely pathogenic

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