disease as well as phenotypic aspects of long-term infantile Pompesurvivors. We report a series of 9 (7 M, 2 F) of the oldest infantilePompe survivors treated with ERT ranging from 4 to 10 years of age. Allpatients had symptom onset within the first 6 months of life, includingsevere cardiomyopathy. Median age at start of ERT was 4.6 months(range 0.3 - 6.3 months). Patients received alglucosidase alfa at 20 -40 mg/kg biweekly and all patients tolerized to ERT. At most recentfollow-up, all 9 patients were ambulatory and none required invasiveventilation. The majority of patients had some residual motorweakness (neck flexor and dorsiflexor weakness, myopathic facies).Additional findings included ptosis, hypernasal speech, sensorineuralhearing loss and osteopenia. Despite hypernasality and some expres-sive language delays, these children remain cognitively intact. Thisstudy provides a contextual basis for understanding the emergingphenotype and relevant issues in clinical management. Continuedsystematic follow-up is necessary to better characterize this emergingphenotype and to allow for improved patient management.

doi:10.1016/j.ymgme.2010.11.123

Eliglustat, an investigational oral therapy for gaucher disease type1 (GD1): Phase 2 results and assessment of patient responses andachievement of established therapeutic goals after 2 years oftreatment

Ana Cristina Pugaa, Elena Lukinab, Nora Watmanc, Marta Dragoskyd,Marcelo Lastrebnerd, Gregory Pastorese, Elsa Avila Arreguinf, HannaRosenbaumg, Mici Phillipsh, aGenzyme Corporation, Naarden, Naarden,The Netherlands, bNational Research Center for Haematology, Moscow,Russia, cHospital Ramos Mejia, Buenos Aires, Argentina, dInstitutoArgentino de Diagnostico y Tratamiento, Buenos Aires, Argentina, eNewYork University, New York, USA, fInstituto Mexicano del Seguro Social,Hospital de Especialidades, Col. La Raza, Mexico, gRambam MedicalCenter, Haifa, Israel, hSha'are Zedek Medical Center, Jerusalem, Israel

Introduction: Patient responses to eliglustat (USAN: eliglustattartrate) were evaluated after 2 years of treatment with reference toevidence-based therapeutic goals for GD1 disease parametersestablished for intravenous enzyme replacement therapy withimiglucerase (Pastores et al., Semin Hematol. 2004).

Description: Study entry criteria required splenomegaly withthrombocytopenia and/or anemia. Efficacy endpoints included meanchanges from baseline in spleen and liver volumes and hemoglobinand platelet levels. Also evaluated was achievement of therapeuticgoals for spleen volume (≥50% decrease and/or reduction to≤8multiples of normal [MN]); liver volume (≥20% decrease and/orreduction to≤1.5 MN); hemoglobin (≥11.0 g/dL for women, ≥12.0 g/dL for men); and platelets (≥120,000/mm3 if baseline was≥60,000/mm3, ≥50% increase if baseline was <60,000/mm3).

Results: In patients completing 2 years of treatment (20/26), therewere statistically significant increases in hemoglobin and platelet levelsand decreases in spleen and liver volumes. Therapeutic goals were metby 90% of patients for spleen, 95% for liver, 95% for hemoglobin and 60%for platelets. Overall, after 2 years of treatment, 85% (17/20) of patientsmet established therapeutic goals for≥3of the 4parameters. Three-yearresults will be available for presentation.

Conclusion/Discussion: Eliglustat has shown promising efficacy as apotential oral substrate reduction therapy for GD1. Improvements inhematologic parameters and organ volumes after 2 years indicatethat most patients treated with eliglustat met established therapeuticgoals for GD1, showing progressive, clinically meaningful responsesin multiple organ system.

doi:10.1016/j.ymgme.2010.11.124

SBC-102, a recombinant enzyme replacement therapy correctsclinically relevant phenotypic abnormalities in a rat model oflysosomal acid lipase deficiency

Anthony Quinna, Mark Leavitta, Wei Hua, Alex Harveya, MichaelChena, Tamas Nagyb, Angela Lentsa, Emelie Balmesa, Sara Mathewsa,aSynageva BioPharma Corp, Lexington, MA, USA, bUniversity of Georgia,Athens, GA, USA

Lysosomal Acid Lipase (LAL) Deficiency is a rare recessive lipidstorage disorder that results in the accumulation of lipids, predomi-nately cholesterol esters (CE) and triacylglycerols (TAG), in varioustissues, particularly the liver, leading to severe liver dysfunction andthe GI tract, leading to growth failure. Early onset disease (Wolman)is characterized by profound malabsorption and is usually fatalwithin the first year of life. In later onset disease (CESD),hepatomegaly and type II hyperlipidemia dominate the clinicalpicture. We have carried out a detailed phenotypic analysis of apreviously described rat model of LAL deficiency and investigated theeffects of rhLAL (SBC-102) in this model. Wild type-WT and LALdeficient-LAL-D rats are the same weight at 3 weeks of age and by8 weeks LAL-D rats weigh only 50% of WT. Lipid profiling demon-strated decreased serum lipids including CE and TAG in LAL-D rats.Differences between WT and LAL-D rats and the normalizing effectsof SBC-102 at week 8 after 4 weeks of dosing are summarized below.Group Body weight (g) Organ weight as % BW Liver SpleenDuodenum JejunumLAL-D Rx placebo 102 11.85 0.84 1.11 3.8LAL-DRx SBC-102 171 5.57 0.32 0.48 2.0WT 201 4.75 0.25 0.3 1.61Group AST(U/L) Serum nmolg-1 Liver lipid content ugmg-1 tissue CE TAG CETAGLAL-D Rx placebo 324 1045 494 2.44 30.8LAL-D Rx SBC-102 1081420 804 0.79 14.2WT 96 1836 1241 0.2 14.1Conclusions: SBC-102decreases lipid substrate accumulation in key tissues and correctsclinically relevant phenotypic abnormalities in a rat model.

doi:10.1016/j.ymgme.2010.11.125

Measuringpatient experiences in fabrydisease: validationof the FabryOutcome Survey (FOS) paediatric health and pain questionnaire

Uma Ramaswamia, Catharina Whybrab, Gisela Kalkumb, GuillemPintos Morellc, Rosella Parinic, Marianne Rohrbachd, Ingela Wiklunde,Mireia Raluye, Michael Beckd, Donald Stullf, aAddenbrooke's Hospital,Cambridge, UK, bUniversity of Mainz, Germany, cUniversity Hospital,Badalona, Spain, dUniversity Children's Hospital, Zurich, Switzerland,eUnited BioSource Corporation, London, UK, fUnited Biosource Corpora-tion, Bethesda, MD, USA

Introduction: Common symptoms for children with Fabry Disease(FD) – pain or burning sensations in the extremities – can only beassessed by patients using a valid instrument. To date, no suchinstrument exists.

Methods: A 28-item measure of the children's symptoms andexperience with FD – the FOS Paediatric Health and Pain Ques-tionnaire – was developed by the FOS Paediatric Working Group. Thisnew measure was used in the Fabry Outcome Survey, a registry for allpatients with Fabry disease who are receiving agalsidase alfa, or arenot treated with enzyme replacement therapy (ERT). A battery ofpsychometric analyses was performed to assess the measurementproperties of this new instrument.

Results: Eighty-seven children (ages 4-18 years) completed thequestionnaire for these analyses. Twenty-three items in threesubscales of the questionnaire emerged: Pain associated with heator exertion, pain associated with cold, and abdominal pain andfatigue symptoms. Internal consistency reliability for all three

Abstracts / Molecular Genetics and Metabolism 102 (2011) S3–S47 S37