alfa (0.2 mg/kg) or agalsidase beta (1.0 mg/kg) infusions q2wks if they meet the Canadian treatment guidelines. Due to a severe shortage of agalsidase beta, 36 patients, (24 M, 12 F, mean age 50.2± 12.7 yrs) were switched to agalsidase alfa in May 2010 from agalsidase beta (mean 70.3±25.1 mos, includes time pre CFDI). We report outcomes after a mean of 15.1±1.9 mos with agalsidase alfa. This group was characterized by advanced disease (dialysis or transplant 27.8%, chronic kidney disease 42.9% of the rest, hyperten- sion 47.2%, LVH 68.8%, pacemaker 33.3%, and stroke or TIA 25%). Clinical parameters were compared between the time of switch and the latest 6 monthly visit. No differences were seen between the ERT periods in mean blood pressure, eGFR (MDRD), CKD stage, proteinur- ia and MSSI. Echocardiography was available pre and post switch in 20/36 (55.5%); mean LVM index, posterior wall thickness and NYHA grade did not differ between pre and post switch. Only septal wall thickness (SWT) differed (1.40 cm pre vs. 1.49 cm post p=0.032). These results suggest that in the short term, there is little detectable clinical change after switching patients with Fabry disease from agalsidase beta to agalsidase alfa in the CFDI. Whether the SWT increase is due to disease progression or switch of ERT is unknown. doi:10.1016/j.ymgme.2011.11.174 Cell-Based Evaluation of Small Molecules for Treatment of Pompe Disease Wendy Westbroek a , Ann Marie Gustafson a , Juan Marugan b , Jingbo Xiao b , Wei Zheng b , Arash Velayati a , Ehud Goldin a , Ellen Sidransky a , a National Human Genome Research Institute, Bethesda, Maryland, USA, b National Human Genome Research Institute, NIH Chemical Genomics Center, USA Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA). Mutations in GAA impair the breakdown of glycogen, causing storage in enlarged lysosomes. Cardiac and skeletal muscles are severely affected, causing impaired breathing and mobility. More than 100 disease-causing mutations in GAA have been identified, some of which retain enzymatic activity in vitro, but are not trafficked to the lysosome. Instead the misfolded GAA stays in the endoplasmic reticulum (ER) and eventually undergoes protea- some-mediated breakdown. Enzyme replacement therapy with alglucosidase alfa improves clinical outcome, but does not reverse all disease manifestations. It was postulated that small molecules which aid in protein folding, and translocation of enzymes to lysosomes could provide an alternate therapeutic strategy. We identified several promising non-inhibitory compounds for GAA from a chemical compound library by in vitro assays. For further biological evaluation, we developed an in vivo cell-based immune-fluorescence cytochemistry assay to assess chaperone capacity. Translocation was evaluated by measuring the extent of co-localization between GAA and Cathepsin-D, a lysosomal marker, using laser scanning confocal microscopy. Using a GAA- specific antibody, control fibroblasts showed specific GAA staining in the lysosomes, while fibroblasts from patients with Pompe disease lacked this signal. However, after treatment of Pompe fibroblasts with GAA activator, the protein level and translocation of GAA to lysosomes was comparable to control cells. These promising small molecules, identified using an in vivo cell-based assay, merit further evaluation as a potential new therapy for Pompe disease. doi:10.1016/j.ymgme.2011.11.175 The Mild Side of MPS Disorders: Are These Cases Being Missed by Urine Screening and Other Common Diagnostic Methods? Klane White a , Nancy Mendelsohn b , Susan Hale a , Olson Rebecca b , Ward Tim c , a Seattle Children's Hospital, Seattle, WA, USA, b Children's Hospitals and Clinics of Minnesota, Minneapolis, MN, USA, c Greenwood Genetic Center, Greenwood South Carolina, USA Morquio syndrome type A (MPS IVA) and Maroteaux-Lamy syndrome (MPS VI) are autosomal recessive lysosomal storage diseases (LSD).Corneal clouding, short stature and preservation of intellectual function are common to both disorders. MPS IVA patients typically present with spine and hip abnormalities, genu valgum, pectus carinatum and joint laxity, while MPS VI patients present with spine and hip abnormalities, joint restriction and hepatomegaly. The initial laboratory testing for both disorders is a urine glycosamino- glycan (GAG) screen looking for increases in total urinary GAG or for specific elevations in keratan sulfate (MPS IVA) or dermatan sulfate (MPS VI). Here we present three MPS cases (2 with MPS IVA and 1 with MPS VI) with normal or mildly elevated urine GAG and mild clinical presentations. Hip dysplasia and joint pain were common features to all patients. Collagenopathies and other skeletal dysplasias were ruled out in each case. In the absence of strong urine GAG findings, leukocyte enzyme analysis was performed with low activity found for either N-acetyl-galactose-6-sulfatase or arylsulfatase B. Mutation analysis was used to confirm the diagnosis and has been completed in three patients. Two mutations were identified in one of the MPS IVA patients (p.R259Q/p.G301C) while another had only one mutation identified (p.G301C) and no duplication/deletions found. The MPS VI patient was homozygous for the known pathogenic p.Y210C change. These cases question the utility of urine based testing for mild MPS cases and highlight the difficulties in making these diagnoses. doi:10.1016/j.ymgme.2011.11.176 Assessing the Reliability, Validity, and Responsiveness to Change of the Hunter Syndrome – Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Ingela Wiklund a , Mireia Raluy a , Yvonne Jangelind b , David Whiteman b , Anne Conway c , Francis Pang b , Donald Stull a , Wen-Hung Chen d , a United BioSource Corporation, London, UK, b Shire HGT, Nyon, Switzerland, c Shire HGT, Lexington, MA, USA, d United BioSource Corporation, Bethesda, MD, USA Objectives: Hunter syndrome (HS) is a rare X-linked progressive multi-systemic lysosomal storage disease. The patient and parent versions of the multidimensional domain HS-FOCUS questionnaire were used to monitor the safety and efficacy of enzyme replacement therapy (ERT) in clinical trials. The objective was to validate the HS- FOCUS according to the FDA PRO Guidance. Methods: HS-FOCUS data collected in a 53 week placebo-con- trolled trial was used to evaluate item performance, reliability, validity, and responsiveness. Results: Altogether, 49 children above 12 years old and 84 parents completed the HS-FOCUS at baseline and follow up visits. High percentage of lowest item response (>60%) and high average inter- item correlations suggested some item redundancy. The internal consistency met the >0.70 criteria for all domains in parents and patients, except the Sleeping domain in patients. The test-retest reliability was >0.70 for most domains except Sleeping and School/ Work domains in patients, and except Satisfaction and Botheredness domains in parents. The construct validity showed moderate to high Abstracts / Molecular Genetics and Metabolism 105 (2012) S15–S69 S65