body disease potentially explaining the increased incidence ofcognitive impairment in GBA associated PD.

doi:10.1016/j.ymgme.2010.11.139

A new pain assessment tool for Fabry disease

Katherine Simsa, Virginia Clarkea, Gregory Hungb, Dana Martinc,aMassachusetts General Hospital, Cambridge, MA, USA, bMassachusettsCollege of Pharmacy & Health Sciences/Genzyme Corporation MedicalAffairs Fellowship, Worcester/Cambridge, Massachusetts, USA, cGenzymeCorporation, Cambridge, Massachusetts, USA

Background: Fabry disease is an inherited metabolic disorder dueto deficiency of the lysosomal enzyme -galactosidase A, leading topathologic accumulation of glycosphingolipids, primarily globotriao-sylceramide (GL-3). Accumulation occurs in the vascular endotheliallysosomes of multiple organs including the heart, peripheral andcentral nervous system, and kidneys. Early disease manifestationsinclude chronic pain- related symptoms (acroparesthesias andgastrointestinal disturbances) that impact health- related quality oflife (HRQoL). The Brief Pain Inventory (BPI) Short Form is astandardized instrument often used to assess pain in Fabry patients.The effectiveness of this tool in Fabry disease is limited becausequestions focus only on symptoms experienced within the previous24 hours.

Hypothesis: A Fabry-specific pain assessment tool may enablehealthcare providers to better understand inter-patient variability ofpain symptoms and effects on HRQoL.

Results: We have designed a Fabry pain inventory with aim ofgathering data more appropriate to the small-fiber neuropathic andgastrointestinal dysmotility pain experienced by Fabry patients. Thequestionnaire was piloted with 10 Fabry patients from the Massa-chusetts General Hospital (MGH), Neurogenetics Clinic. Resultsrevealed significant inter-patient variability in the timing, frequencyand duration of pain symptoms that would not have been ascertainedwith the standard BPI pain recall questions focused on the previous24 hours.

Discussion: Initial data supports the hypothesis that a Fabry-specific pain assessment may assist healthcare providers to betterunderstand pain-related symptoms in this population. This toolshould enable optimization of therapeutic interventions and improvepatient outcomes. Further development and validation of the MGHFabry Pain Inventory is underway.

doi:10.1016/j.ymgme.2010.11.140

The evolving and expanding role of patient advocate groups andconsortiums of PAGs in research, funding, policy, awareness,and support

Dean Suhr,MLD Foundation, RDCRN/LDN CPAG co-chair, West Linn, OR, USA

Patient Advocate Groups (PAGs) work closely with, and support,medical researchers, however, as independent charities and non-profits, they have the flexibility and responsibility to pursue manyother activities. This status can afford them a level of trustedcommunication, influence, and rapport with individual researchers,industry, institutions, regulators, policy makers, and of course,families, that researchers and industry cannot attain. PAGs must riseto this challenge and fill this gap as representatives for their disease,disease umbrella(s), and as members of the rare disease community.This paper will discuss the evolving and expanding role of PAGs in

research, education, awareness, policy, with other PAGs, and withfamilies. We will explore how increased access to information,communication, and networking facilitated by the Internet increasesthe ability of PAGS to expand these roles and efficiencies. Theevolving role and potential of a consortium of PAGS, such as the LDNdriven Coalition of Patient Advocate Groups (CPAG), will be as apresented as a powerful potential force well beyond simply endorsing& funding research. A unified coalition of PAGS can have a significantimpact on public policy and awareness which can increase outside“push” pressure and support to increase and fund research, ratherthan research relying on the traditional hamster wheel “pull” of grantand funding cycle applications. Finally, since a PAG has a primaryresponsibility to families affected by a particular disease, we willdiscuss how a strong coalition of PAGs can make an individual PAGmore efficient and effective in this role.

doi:10.1016/j.ymgme.2010.11.141

Lipidomics of Gaucher disease: Substrate composition and natureis dependent on tissue/region and acid β-glucosidase mutations –phenotypic and therapeutic implications

Ying Sun, Wujuan Zhang, Brian Quinn, Kenneth Setchell, You-Hai Xu,Gregory Grabowski, Cincinnati Children's Hospital Medical Center,Cincinnati, OH, USA

Glucosylceramide (GC) is a precursor of over 300 complexglycosphingolipids that are important in biologic processes. Also,numerous species of GC with varying fatty acyl chain lengths impactits biological activity/role. In Gaucher disease, autosomal recessivelyinherited mutations in the GBA1 locus, encoding acid β-glucosidase(GCase), have result in defective cleavage of GC and glucosyl-sphingosine leading to heterogeneous manifestations in the visceraland neuronal tissues. To characterize mutation, tissue and age-dependent accumulation of GC species, tissues/regions from Gaucherdisease mouse models carrying mutations, D409H/D409H (9 H),V394L/V394L (4 L), D409V/D409V(9 V) and D409V/null (9 V/null),were analyzed by LC-MS/MS. Of those mutants, 9 V/null mice showedthe progressive and preferential age-dependent accumulations ofdifferent GC species with age, e.g., GC(24:0) in the lung and GC(16:0)in the liver, but no preferential splenic storage. The increases of GC(24:0) in 9 V/null lung differed greatly from the wild type GC species.The 9 V, 9 H and 4 L mice did not show preferential lung GC speciesaccumulation. Treatment of 9 V/null mice with recombinant humanGCase reduced storage of all GC species in the liver. In a neurono-pathic Gaucher disease model, 4 L;C* mice, brain glucosylsphingosinewas greatly increased, but was only slightly increased in 9HC* mice, amore visceral disease model. These results demonstrate age, tissue/regional, and mutation-specific quantitative differences in GC andglucosylsphingosine accumulation with preferential substrate storagein specific tissues. Such differential GC species and glucosylsphingo-sine accumulations likely contribute significantly to the mutational-dependent tissue/regional expression of Gaucher disease phenotypes.

doi:10.1016/j.ymgme.2010.11.142

Sf9 cell vesicle-mediated correction of cystine storage in cystinoticfibroblasts and sialic acid storage in infantile sialic acid storagedisease fibroblasts

Jess Thoene, Marc Witcher, Jodi Mullet, Q56University of Michigan, AnnArbor, MI, USA

Abstracts / Molecular Genetics and Metabolism 102 (2011) S3–S47S42