The juvenile onset form of Batten disease (JNCL) is the result of mutations in the CLN3 gene but the underlying disease mechanisms remain poorly understood. Cln3-/- mice are proving to be a valuable resource for investigating the consequences of CLN3 mutation upon the CNS displaying both pathological and neurological signs of the disorder including visual failure and motor coordination deficits. We have subsequently detailed evidence of an autoimmune component to this disease. We have utilized both genetic and pharmaceutical approaches to investigate the impact of the autoimmune response in Cln3-/- mice. The Cln3-/- mice were crossed with the B-cell deficient μMT mouse to generate mice that were immune deficient through the inability to produce B-cells as well as lacking a functional CLN3 protein. These mice were incapable of generating endogenous IgGs. Importantly, Cln3-/- mice lacking B-cells showed an amelioration in the characteristic deterioration of motor skills which we attribute the fact we saw a decrease in the inflammatory response as well as immune mediated pathologies. Mycophenolate motefil (MMF), inhibits inosine monophosphate dehydrogenase, an enzyme involved in the de novo pathway of purine synthesis in proliferating B and T lymphocytes, thereby attenuating any immune response. We there- fore used MMF to treat Cln3-/- mice as a pharmacological means to attenuate the immune response. Similar to the genetic ablation of B- Cells we saw a diminution of both inflammatory response as well as immune mediated pathologies. Remarkably this drug treatment also improved the motor function of Cln3-/- mice.Our data provide evidence for a positive effect of MMF treatment upon the neurologic, reactive and neurodegenerative phenotypes of murine JNCL. doi:10.1016/j.ymgme.2010.11.117 Eliglustat for Gaucher disease Type 1 (GD1): Safety results from a Phase 2 study after 2 years of treatment M. Judith Peterschmitt a , Elena Lukina b , Nora Watman c , Marta Dragosky d , Marcelo Iastrebner d , Gregory Pastores e , Elsa Avila Arreguin f , Hanna Rosenbaum g , Mici Phillips h , Mathilde Kaper a , Dominique Bertin-Millet a , Ana Cristina Puga a , a Genzyme Corporation, Cambridge, MA, USA, b National Research Center for Haematology, Moscow, Russia, c Hospital Ramos Mejia, Buenos Aires, Argentina, d Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires, Argentina, e New York University, New York, USA, f Instituto Mexicano del Seguro Social, Hospital de Especialidades, Col. La Raza, Mexico, g Rambam Medical Center, Haifa, Israel, h Sha'are Zedek Medical Center, Jerusalem, Israel Introduction: Two-year safety results are available from a Phase 2 study of eliglustat (USAN: eliglustat tartrate). Description: Safety monitoring included adverse event (AE) reporting and scheduled laboratory, electrocardiographic, neurologic, and nerve conduction velocity (NCV) evaluations. Results: Twenty-six patients enrolled; 20 completed 2 years of treatment. Six patients discontinued during the first year for pregnancy (3 patients); progression of pre- existing (noted retro- spectively on baseline MRI) femur osteonecrosis (1 patient); and asymptomatic non-sustained ventricular tachycardia (NSVT) de- tected only by telemetry after the first dose with undetectable plasma drug levels at the time of the event (2 patients). During 2 years, 23 patients reported 126 AEs; 76% were mild. The largest number (33/126) was reported during the first 3 months. The most common AEs were viral infections (6 patients), and urinary tract infections, increased blood pressure, and abdominal pain (3 patients each). Six patients had 8 mild treatment-related AEs: abdominal pain (2 patients), diarrhea (2 patients), palpitations (1 patient), asympto- matic NSVT (1 patient), headache (1 patient), and asymptomatic peripheral neuropathy detected by NCV at 18 months in 1 patient who had a history of symptomatic peripheral neuropathy. Two patients with cardiac valve disease experienced NSVT: one was considered possibly treatment-related in a patient who remained hospitalized for prolonged (uneventful) cardiac monitoring, and the other was considered remotely/unlikely treatment-related in a patient who showed NSVT on Holter monitoring 2 months after treatment ended. Three-year safety results will be available for presentation. Conclusion/Discussion: Eliglustat was well-tolerated. No safety- related trends of concern emerged during 2 years. doi:10.1016/j.ymgme.2010.11.118 MPS I: Age at transplant is associated with better long-term developmental outcomes Michele Poe a , Maria Escolar a , Joanne Kurtzberg b , Hannah Yin a , a UNC, 27599-8185, NC, USA, b Duke Medical Center, US Q31 Background: Hurler's syndrome (the most severe form of mucopo- lysaccharidosis type I) is an autosomal recessive metabolic storage disease caused by a deficiency of alpha-L-iduronidase, which results in the accumulation of heparan and dermatan sulfate substrates (glyco- saminoglycans) in various tissues. The severe phenotypes, in which symptoms begin by two years of age, are characterized by severe, progressive deterioration of the central nervous system, cardiac disease, skeletal abnormalities, corneal clouding, hepatomegaly, and death in childhood. Hematopoietic stem cell transplantation has been shown to be beneficial in treating MPS I. This study examines the relationship between age at transplantation and post-transplant development in four neurodevelopmental domains. Methods: This study follows 45 patients who were given hematopoietic stem cell transplantation for treatment of MPS I. Children were evaluated pre-transplant and every 6-12 months thereafter. Standard scores and developmental quotients were converted to age equivalent scores to allow comparisons among various tests and to identify development of new skills. Motor, cognitive, receptive and expressive language and adaptive behavior were assessed. Results are compared to norms of typically developing children. Developmental curves are generated and analyzed in relation to age at transplant as well as baseline evaluations. Results: Age at time of transplant is a strong predictor of development in children with Hurler's disease. Conslusions: The degree of neurological disease at the time of hematopoietic stem cell transplantation is a strong predictor of longitudinal outcomes. These results emphasize the urgency the identification of MPS I through newborn screening and the timeliness of treatment once the disease is identified. doi:10.1016/j.ymgme.2010.11.119 MPS II: developmental outcomes after hematopoietic stem cell transplantation Michele Poe a , Maria Escolar a , Joanne Kurtzberg b , Paul Szabolcs b , Vinod Prasad b , Suhag Parikh b , Josh Holt a , a UNC, 27599-8185, NC, USA, b Duke Medical Center, US Q32 Objective: Mucopolysaccharidosis II (MPS II) is an X-linked disorder caused by deficiency of iduronate-2-sulfatase, resulting in progressive Abstracts / Molecular Genetics and Metabolism 102 (2011) S3–S47 S35