ALFA-L -IDURONIDASE GENE MUTATIONAL ANALYSIS OF 10 EGYPTIAN PATIENTS Ibrahim M 1 , Gouda A 1 , Fateen E 1 , Amr K 2 , Cooper A 3 1 1Biochemical Genetics Departments, Natio, Giza, Egypt 2 2 Molecular Genetics Departments, Nation, Giza, Egypt 3 3Willink Biochemical Genetics Unit , Man, Manchestar, United Kingdom Introduction: The various disorders of mucopolysaccharidosis (MPS) share many clinical features. MPS-I is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme α-L-iduronidase. Aim of work: Diagnosis of MPS-I among suspected cases referred to Biochemical Genetics Department. Detection of the mutation in the αiduronidase gene among some of the diagnosed Egyptian patients. Subjects and Methods: 10 patients were included; each one was subjected to quantitative determination of urinary GAGs, two dimensional electrophoretic separation, assay of α-L-iduronidase enzyme activity and mutational analysis. Results: Mutational analysis proved that 1 patient was homozygous for the mutation E299, 1 patient homozygous for the mutation C 593 ins 4 del 8 and another one for P533R. MPS-I mutations were not detected in the 4 other patients. 3 novel mutations (c. 854delC in exon 6, T141S in exon 4, and IVS2+6c>t) and G51D in exon 1 were detected. In addition; 9 sequence variants including 5 previously unreported polymorphisms (N73H, N297N, R363S, IVS10 (3025) g>t, and IVS11 (3318) c>a) were identified. Conclusion: Sequencing of the whole gene of α-L-iduronidase is needed to diagnosed patients to detect the commonest mutations among our population and their correlation with the response to enzyme replacement therapy when available. We present a primiparous 37-year-old woman with Mucopolysaccharidose type I, Scheie disease (MPSI-S) who continued to receive enzyme replacement therapy (ERT) with Aldurazyme in a dose of 100 I/U every week during pregnancy. Fetal development was normal and amniocentesis showed a normal karyoptype and enzyme activity for alpha-L-Iduronidase (IDUA). The patient underwent regular cardiac evaluation by echocardiography, which showed moderate mitral and aortic valve regurgitation with normal LV function. At the end of pregnancy she developed signs of pre-eclampsia with hypertension and albuminuria, which was treated with intravenous magnesium sulfate. After a gestational period of 37 weeks and 5 days a Caesarean section was performed and a healthy boy was born. After delivery the patient was admitted to the ICU because of congestive heart failure. Echocardiography revealed significant aggravation of the preexisting mitral and aortic valve regurgitation. After rigorous treatment, the patient recovered without sequelae and was discharged eight days after delivery. This case report indicates that ERT with Aldurazyme can be administered safely during pregnancy, but demonstrates that pregnant MPS I patients should monitored closely especially during the last months of pregnancy because of hemodynamic changes that may occur. Methods: A nationwide survey was conducted in Japan to collect clinical data of the patients with MPS II who received HSCT. The ability of daily life (ADL), joint mobility, height, IQ, MRI lesions, regurgitations of heart valves, and urinary glycosaminoglycans (GAG) were analyzed at the baselines and at the most recent visit in each patient. Results: The records of 26 patients collected from 8 distinct hospitals. The follow-up period was from 5 years 5 months to 16 years 3 months (mean, 9 years 6 months). ADL was maintained almost around baseline levels, joint mobility was improved, growth of height was better than untreated patient cohort. Cribriform changes and ventricular dilatation in brain MRI were improved in 9 and 4 patients, respectively. No improvement was shown in brain atrophy. Valvular regurgitations were diminished in 20 valves out of 66 valves, while worsening was observed frequently in the patients transplanted at older ages. The values of urinary GAG were remarkably lower in HSCT-treated patients than age-matched untreated patients. Conclusion: HSCT is effective and worthwhile in MPS II patients with both of attenuated and severe forms. Background. Mucopolysaccharidosis type II is an X-linked, progressive lysosomal storage disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In recent years, clinical trials and overall experience with enzyme replacement therapy (ERT) have been shown to clinically benefit patients with considerable preexisting disease, but no data exists on the effect of beginning ERT before the onset of significant clinical signs of disease. Material and Methods. We present the 3-year follow-up of a boy with MPS II who had idursulfase therapy initiated at the age of 3 months and compare his clinical course to his healthy twin brother. Results. After 3 years of treatment, the patient has not developed any clinical manifestations of MPS II. The most impressive findings were the preservation of normal ranges of movement for most joints, cardiac valves and facial appearance for our patient. The only difference when compared with his healthy twin brother was lower IQ and mild deformity of one vertebrae. Conclusion. We suggest that early treatment of MPS II may significantly delay or prevent the onset of the major clinical signs, substantially modifying the natural history of the disease. Introduction: Mucopolyssacharidosis type III (MPS III), known as Sanfilippo syndrome results from the deficiency of several enzymes needed to break down the glycosaminoglycan (GAG) heparan sulphate, which is particularly important in the central nervous system. MPS IIIC results from deficiency of acetylCoA:alpha-D-glucosaminide acetyltransferase. No specific treatment is available and is therefore limited to the management of symptoms. Genistein an isoflavone that inhibits glycosaminoglycans synthesis has been tried in some patients with MPS IIIA. Case report: We report a seven year old girl presenting with dysmorphia, mild developmental delay mainly of speech, hyperactivity, hepatomegaly high liver enzymes and mild bone abnormalities. Biochemical and molecular analysis showed increased urinary heparin sulphate, no residual activity in PBTL and two causal splicing mutations confirming the diagnosis of type C Sanfilippo disease. Having started genistein supplementation (10 mg/kg/day, in two daily doses) a significant decrease of GAGs and heparan sulphate in the urine were noticed three months later. This decrease was not sustained at a 6 month control evaluation and did not seem to have any clear clinical benefit. Conclusions: Although genistein may decrease the excretion of GAGS in the urine in patients with MPSIII, this effect may be transient and have no effect on symptoms.