Mutation analysis of the iduronate-2-sulfatase gene among Egyptian patients with hunter syndrome / Nouran Mohammed Sedky ; Supervised Mona Salem Khalil , Mona Lotfi Essawi , Nahed Mohamed Ibrahim

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

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked disorder caused by mutations in the gene which controls the production of the enzyme iduronate-2-sulfatase (IDS). It belongs to subgroup of diseases called mucopolysaccharidoses caused by lysosomal accumulation. It is a rare disease worldwide, with an incidence of 0.3{u2013}0.7 per 100,000 live births. The primary defect is a mutation on the IDS gene which causes a deficiency in the activity of the lysosomal enzyme. The enzyme IDS catalyses one of the steps in the catabolism of glycosaminoglycans (GAGs), resulting in the accumulation of heparan and dermatan sulphate in different tissues and organs mainly in connective tissue, liver, spleen, and brain, with excretion of large amounts of them in urine. The clinical spectrum includes mild, intermediate, and severe variants. The patients clinically are characterized by coarsening of facial features, bone and joint abnormalities, short stature, changes in heart, respiratory system, hearing and vision, and in more severe forms by disturbed motor function, progressive learning difficulties and behavioral abnormalities. To date, more than 500 different mutations associated with MPS type II have been identified. The study was conducted on sixteen Egyptian male patients from fifteen unrelated families with Hunter syndrome. Eleven patients (73.3%) had hepatosplenomegaly. Seven patients (46.8%) had ENT problems mostly due to enlarged adenoids. Three patients (20%) had CNS abnormality and delayed IQ. Five novel and four previously reported mutations were detected in nine of our patients

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