Yano S 1 , Moseley K 1 1 Genet, Pediatr, Univ S California, Los Angeles, United States Background: Progressive cardiovascular changes have been known as one of the major causes of death in patients with mucopolysaccharidosis (MPS). All types of MPS have been reported to present with cardiovascular manifestations. Evaluation of endothelial function (EF) by flowmediated dilation (FMD) of the brachial artery has been studied and endothelial dysfunction (ED) characterized by decreased percent mediated dilatation was demonstrated in individuals with risk factors for atherosclerosis. Close relation of EF in coronary and brachial artery has been demonstrated. Studies to evaluate peripheral vascular EF with finger arterial pulse wave amplitude (PWA) with a finger plethysmograph (PAT) have been performed and showed that PAT hyperemia and FMD were significantly correlated. Objectives: To evaluate coronary artery ED in MPS patients for early detection of coronary artery lesions. Material and Methods: Finger arterial PWA with a PAT device (Endo-PAT2000) was used to evaluate coronary EF. Total of 17 patients were studied: MPS-I (11), II (2), III (2) Twenty-seven MPSpts (6MPS I, 16 MPS II, 5 MPS VI) on ERT were evaluated regarding urinary glycosaminoglycans(ur.GAGs) and the passive articular range of motion. Pts' mean age: MPS I 30.5 years(y)(range 16.7-44.0); MPS II 17y (11.3-29.9), MPS VI 7.4y (4.5-9.4) . ERT mean duration: MPS I 7.5y (6.3-8.7); MPS II 4.8y (3.2-7.1); MPS VI 3.7y (2.4-5.2) . ERT resulted in a mean reduction in ur.GAGs of 89% for MPS I (78.9-96.7); 76.1% for MPS II (30.4-97.2); 65.4% for MPS VI (37. 5-83.4 ). All the pts increased shoulder abduction: mean gain of 27.9degrees in MPS I; 20.8 in MPS II; 8.5 in MPS VI. In MPS I there was a hip mobility improvement (mean 11.2degrees) and a moderate improvement of wrists (6.7degrees) and elbows (4.9degrees). In MPS II there was a stabilization for each joint (gain of 2-3degrees), except for the foot (−1.6). In MPS VI, there was a gain of 2 degrees in foot mobility, there was a 1-3degree loss for the other joints. ERT is effective in decreasing ur.GAGs and in improving shoulder abduction. The best improvement was in MPS I pts (the ones treated longer), whereas there was a joint mobility stabilization in MPS II and MPS VIpts MPSII is the most prevalent type in Brazil with 30% of the cases (Rede MPS Brasil, 2010) , but in MG the most common is MPSI with almost 35% of the MPS. Most patients have classic phenotypes, but rare symptoms as heart aneurysm of the tip of the left ventricle and liver cirrhosis were observed in MPSII. As a differential diagnosis, GM1 gangliosidosis, mucolipidosis II, Geleophysic dysplasia, Dyggve-Melchior-Clausen syndrome, congenital hypothyroidism and Costello syndrome patients were sent to HC-UFMG. Enzyme replacement therapy has been indicated to most patients with MPSI, II and VI. One MPSI patient received successful stem cell transplantation 15 months ago at age of 1 year. Background: Mucopolysaccharidosis I (MPS I) is caused by a deficiency of α-L-iduronidase (IDUA), mainly due to nonsense mutations. Stop codon read through (SCRT) is an alternative to increase enzyme activity by the suppression of a premature stop codon. Objective: To treat MPS I fibroblasts with geneticin and chloramphenicol, which were described to induce misreading. Methods: Fibroblasts from three MPS I patients (p.W402X/p.W402X, p. Q70X/c.1739 G>T, p.R89W/p.W402X) were treated with geneticin (200ug/mL), chloramphenicol (200ug/mL) or had no treatment (n=4/ group). IDUA activity was measured by fluorimetric assay and mRNA expression by quantitative PCR. cDNA sequencing of compound heterozygous was performed. Statistical analysis was done using Friedman with pairwise compairisons (differences: p<0.05). Results: Geneticin was not able to enhance IDUA activity or expression and chloramphenicol enhanced 100-fold IDUA activity on compound heterozygous fibroblasts. cDNA sequencing showed that only the missense allele was being amplified. Conclusion: Nonsense alleles are probably being target to nonsense-mediated mRNA decay (NMD). Thus, positive response to SCRT is dependent on the patient's genotype and on the efficiency of NMD. Chloramphenicol apparently acts through a mechanism other than SCRT. This drug may be used ancillary to enzyme replacement therapy, as it is able to cross the blood brain barrier.