268 Neuroradiological brain phenotype in mucopolysaccharidosis type II patients from 5 European countries Igor Nestrasil a , Carol Nguyen a , Manuela Vaneckova b , Andrea Burgetova b , Lenka Murgasova c , Jiri Zeman b , Danijela Petković Ramadza d , Ivo Baric d , Zsuzsanna Almassy e , Katarina Jurickova f , Vladimir Bzduch f , Anna Tylki-Szymanska g , Martin Magner b , a University of Minnesota, Minneapolis, MN, United States, b Charles University and General University Hospital, Prague, Czech Republic, c Charles University and University Hospital Motol, Prague, Czech Republic, d University Hospital Center, Zagreb, Croatia, e Heim Pal Children's Hospital, Budapest, Hungary, f Comenius University and Children's Faculty Hospital, Bratislava, Slovakia, g The Children’s Memorial Health Institute, Warsaw, Poland Objective: To characterize the neuroradiological brain phenotype in severe and attenuated forms of mucopolysaccharidosis type II (MPS II). Methods: 40 clinical brain MRI scans from 24 males and 1 female with MPS II from 5 European countries were collected. Brain MRIs were analyzed using semi-quantitative MPS Brain MRI rating scale (MPSMRI) specifically developed for MPS population. The scale consists of three domains assessing white matter (WM) hyper- intensities, enlarged perivascular spaces (PVS), and atrophy with ventricular enlargement. Results: The total of 30 scans from 21 subjects (17 severe, 4 attenuated) including longitudinal data sets of 7 subjects (follow-up 2-8 years) have been analyzed. Severe form presented with higher atrophy (p b .0001), ventricular enlargement (VE) (p b .02), and lobar white matter hyperintensities (LWMH) (p=0.06) MPSMRI scores when compared to attenuated cases. There were associations between LWMH and VE scores (R=0.72, p b .001), LWMH and atrophy scores (R=0.70, p b .001) and VE and atrophy scores (R=0.73, p b .001). Longitudinal follow-up revealed a progressive increase in lobar and periventricular white matter hyperintensities, brain atrophy and ventriculomegaly scores, and minimal change in PVS scores. We identified the presence of delayed myelination in 42%, sella turcica enlargement in 81%, middle cranial fossae and posterior fossa CSF collection in 15% and 54% of all cases respectively. Conclusion: We show that white matter disease, enlarged ventricles or hydrocephalus, and brain atrophy are the main and interrelated hallmarks of MPS II, more highly expressed in severe than attenuated forms. All tend to progress overtime whereas the enlarged perivascular spaces show minimal or no progression. Our brain MRI findings propose endpoints suitable for disease registries to track disease outcomes and pinpoint brain abnormalities in MPS II that can serve as potential markers for clinical trials if assessed with a robust quantitative approach. This work was supported by the National Institutes of Health (U54NS065768) and by the RVO-VFN 64165/2012. doi:10.1016/j.ymgme.2017.12.277 269 Expanded analysis of Lyso-GB3 analogues and correlation with total Lyso-GB3 and Fabry status in 59 clinical patients Brian Netzel, Dimitar Gavrilov, Dietrich Matern, Devin Oglesbee, Kimiyo Raymond, Piero Rinaldo, Silvia Tortorelli, Matthew Schultz, Mayo Clinic, Rochester, MN, United States Fabry disease (FD) is an X-linked disorder caused by alpha- galactosidse A (AGA) deficiency. Difficulties in FD diagnosis necessitate better tools for differential diagnosis of atypical FD, regardless of age or gender. Monitoring of globotriaosylsphinogosine (Lyso-GB3) has been correlated to genotype, phenotype, and disease severity in FD. Utilizing the metabolome to aid in FD diagnosis, eight Lyso-GB3 “analogs” have been explored. These analogs, identified by mass shifts from Lyso- GB3 during mass spectrometry analysis, have shown promise in FD diagnosis and potential correlation to genotype. We present the analysis of Lyso-GB3, analogs, and serum AGA activity in 59 confirmed FD patients (9 female, 50 male, 18 pediatric), and 214 normal control subjects (86, 128, 48). Total Lyso-GB3: control population (1st-99th percentile, ng/ml): 0.16-0.73; FD males: 1.49-113.82; FD females: 0.81-80.63. Analogs monitored included Lyso-GB3 (-28, -12, -2, +14, +16, +18, +34, and +50amu). Multiple peaks for each analog were noted in the chromatogram, and each was treated as unique. Twenty- three analogs were included, with 22 elevated in all FD specimens. Lyso-GB3 and analog median values and distributions were more elevated in males, though not always significantly (p = 0.005 to 0.950). Interestingly, a clinically suspected FD female with normal enzyme showed elevations in Lyso-GB3 and 20 of 22 analog concentrations, suggesting active FD. Preliminary data suggests that regardless of AGA activity, correlation of Lyso-GB3 is helpful to establish the FD diagnosis. Analog elevations lend credence to their potential in FD diagnosis; however, Lyso-GB3 levels were sufficient to diagnose in these cases. It remains to be determined if analog ratios and variance yield clinically useful information. doi:10.1016/j.ymgme.2017.12.278 270 Renal outcomes with up to 9 years of migalastat in patients with Fabry disease: Results from an open-label extension study Kathleen Nicholls a , Roberto Giugliani b , Raphael Schiffmann c , Derralynn A. Hughes d , Vipul Jain e , Fred Holdbrook e , Nina Skuban e , Jeffery P. Castelli e , Jay A. Barth e , a Royal Melbourne Hospital, Parkville, Australia, b Medical Genetics Service, HCPA/UFRGS, Porto Alegre, Brazil, c Baylor Research Institute, Dallas, TX, United States, d Royal Free NHS Foundation Trust and University College London, London, United Kingdom, e Amicus Therapeutics, Inc., Cranbury, NJ, United States Fabry disease is a rare, genetic lysosomal disorder caused by a deficiency of α-galactosidase A that results in the accumulation of globotriaosylceramide in multiple tissues. It is associated with altered autonomic function, neuropathic pain, and life-threatening renal and cardiac impairment. Gradual deterioration of renal function to end stage renal disease is common in Fabry disease, and treatments must limit progression of renal impairment to improve morbidity and mortality outcomes. Migalastat is an orally administered pharmaco- logical chaperone that binds to, stabilizes, and restores lysosomal trafficking of amenable mutant forms of α-galactosidase A. Patients with Fabry disease who were treated with migalastat during a phase 2 study and completed that study were eligible to enroll in a phase 3 open-label extension (OLE; NCT01458119). Patients received migalastat at varying doses during the phase 2 study, and then migalastat 150 mg every other day (QOD) during the OLE. The average time on migalastat for phase 2 patients who entered the phase 3 OLE (n= 12) was 8.2 years (maximum 9.3 years). Mean (SD) age was 44.3 (10.7) years; 67% were male; mean (SD) baseline eGFR was 103.8 (18.7) ml/min/1.73 m 2 . The mean annualized rate of change in eGFR CKD-EPI over the entire treatment period was -0.67 (95% CI -1.32, -0.02; n=12). When the analysis was restricted to only periods when patients received migalastat 150 mg QOD, the mean annualized rate of change in eGFR CKD-EPI was 0.24 (95% CI -1.7, 2.2; n=11). eGFR generally remained stable with migalastat treatment regardless of sex or baseline proteinuria levels. Abstracts / Molecular Genetics and Metabolism 123 (2018) S15–S153 S105