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Patient Registries to Support Research in Rare Diseases – Experience from the Rare Diseases Clinical Research Network
S54
Abstracts / Molecular Genetics and Metabolism 105 (2012) S15–S69
Many of the mucopolysaccharidoses (MPS) have significant neurological involvement. Hematopoietic stem cell transplantation (HSCT) has positive effects on the CNS in MPS I, but its beneficial effects are unclear in other MPS. Currently, there are no markers for quantitatively monitoring disease progression, or predicting neurological outcomes in MPS. The objective of this study was to evaluate the utility of brain diffusion tensor imaging (DTI) in individuals with MPS II to identify white matter abnormalities that correlate with neurological involvement. DTI acquisitions were performed on a 1.5 T and 3 T MRI system. Parametric maps for fractional anisotropy (FA) and mean diffusivity (MD) were post-processed using vendor software. We examined FA and MD data (signal intensity in selected regions of interest: corpus callosum-genu and splenium; L(R) left(right)-frontal white matter FWM; L(R)-parietal white matter PWM) from four MPS II patients of comparable age. Two patients had severe MPS II (one untreated and one post-HSCT), and two had attenuated MPS II (both post-ERT). Lower FA and higher MD values were noted in the PWM for both severe MPS II patients, with greater involvement in the untreated patient. The two individuals with attenuated MPS II receiving ERT had near-normal FA and MD. HSCT improved DTI abnormalities without improvement of neurological outcome. Attenuated MPS II post-ERT had slowly progressive somatic disease without neurological involvement. In conclusion, these DTI findings are indicative of abnormal axonal and myelin organization in patients with severe MPS II and lack of major FA and MD in the attenuated phenotypes. doi:10.1016/j.ymgme.2011.11.138
Diagnosis of Mucopolysaccharidosis of a Reference Center Laboratory for Inborn Errors of Metabolism (LEIM) - A Brazilian Experience Marina Rezende, MullerKaren Müller, Ana Maria Martins, Vânia D'Almeida, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil Mucopolysaccharidosis (MPS) are inborn errors of metabolism in which lysosomal enzymatic deficiency leads to glycosaminoglycans accumulation in cell lysosomal compartments. This accumulation is the major responsible for the dysfunction presented in heart, muscles, bones and, sometimes, central nervous system. Depending on the enzyme affected, MPS are subdivided in I, II, III, IV, VI, VII and IX types. The general frequency of this disease is 1:25,000, but there is no consistent data about Brazilian population. The experience of our laboratory with this group of diseases is based on receiving, until now, 385 samples of both genders and age between 0 and 65 years old, with clinical suspicion, from all Brazilian states. The samples received were whole blood tubes and/or dried blood spots, material minimally invasive to collect and of relative easy transport, mainly for the dried blood spots. The analyses are performed by fluorimetric methods in dried blood spots or leukocytes samples. We verified the enzymatic activity of alpha-iduronidase, iduronate 2-sulphatase, galactose-6-sulphatase, arylsulphatase B, which is altered in MPS I, II, IV and VI, respectively. Until now, there were 109 patients with positive results (28.3%), being 44 MPS I (40.3%), 6 MPS II (5.5%), 16 MPS IV (14.7%) and 43 MPS VI (39.5%). Our data suggest that MPS are in an under recognized state and the frequency of these group of lysosomal disease can be higher than expected. Supported by: FAPESP, CNPq, CAPES, AFIP and IGEIM. doi:10.1016/j.ymgme.2011.11.139
Patient Registries to Support Research in Rare Diseases – Experience from the Rare Diseases Clinical Research Network Rachel Richesson a, Denise Shereff a, Rebecca Sutphen a, Heather Guillette a, Kate Paulus a, Peter A. Merkel b, Megan Clowse c, Jennifer Harris a, David Cuthbertson a, Renee Leduc a, Jeffrey P. Krischer a, a University of South Florida College of Medicine, Tampa, FL, USA, bBoston University, Boston, MA, USA, cDuke University, Durham, NC, USA Patient registries are an important component in many diseasespecific research agendas. The number of patient registries is rapidly rising. The lack clear specifications for data collected using patient registries represents a significant data standards gap in an explosively growing application area that is important to both the drug development and patient communities. The Patient Registry Item Specifications and Metadata for Rare Diseases (PRISM) library is a collection of questions used in rare diseases patient registries, designed to support the storage and re-use of questions and answers appropriate for use in a wide variety of registries. The use of the PRISM resource facilitates the efficient development of patient registries, and the standardization of patient registries enables the interoperability of health and research data. The PRISM library is being used as a resource in the registry and research activities of the NIH-funded Rare Diseases Clinical Research Network (RDCRN). In particular, the RDCRN Vasculitis Clinical Research Consortium (VCRC) used PRISM to support the rapid development of an online study exploring the fertility and reproductive outcomes of 452 patients with vasculitis. In addition, PRISM is being used to support extensions of the RDCRN Contact Registry (> 8,100 registrants, > 100 rare diseases). The PRISM resource and the RDCRN Contact Registry model can be leveraged by the RDCRN-affiliated Lysosomal Disease Network to support new partnerships between patient advocacy organizations, researchers, and government sponsors that can increase patient participation in research on lysosomal storage diseases, and ultimately drive the evaluation and availability of new therapeutics. Acknowledgements: The [RD] PRISM Library project is funded by the American Reinvestment and Recovery Act. Support for the [RD] PRISM Library project is administered through the National Library of Medicine. (NLM Grant Number 1RC1LM010455-01, an NIH component, and supported by the Office of Rare Diseases Research. The contents are solely the responsibility of the authors and do not necessarily represent the official views of NLM or ORDR or NIH.) The RDCRN Contact Registry is funded by the National Institute for Neurologic Disease and Stroke (NINDS), (NLM Grant Number 7U54-RR019259-02), a component of the NIH, and supported by the Office of Rare Diseases Research. The contents are solely the responsibility of the authors and do not necessarily represent the official views of NINDS or ORDR or NIH. The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. The Vasculitis Clinical Research Consortium (VCRC) has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. The VCRC is part of the Rare Diseases Clinical Research Network (RDCRN). The VCRC Registry is supported by the Vasculitis Foundation, the Churg-Strauss Syndrome Association, and the PAN Research and Support Network.
doi:10.1016/j.ymgme.2011.11.140
Abstracts / Molecular Genetics and Metabolism 105 (2012) S15–S69
Many of the mucopolysaccharidoses (MPS) have significant neurological involvement. Hematopoietic stem cell transplantation (HSCT) has positive effects on the CNS in MPS I, but its beneficial effects are unclear in other MPS. Currently, there are no markers for quantitatively monitoring disease progression, or predicting neurological outcomes in MPS. The objective of this study was to evaluate the utility of brain diffusion tensor imaging (DTI) in individuals with MPS II to identify white matter abnormalities that correlate with neurological involvement. DTI acquisitions were performed on a 1.5 T and 3 T MRI system. Parametric maps for fractional anisotropy (FA) and mean diffusivity (MD) were post-processed using vendor software. We examined FA and MD data (signal intensity in selected regions of interest: corpus callosum-genu and splenium; L(R) left(right)-frontal white matter FWM; L(R)-parietal white matter PWM) from four MPS II patients of comparable age. Two patients had severe MPS II (one untreated and one post-HSCT), and two had attenuated MPS II (both post-ERT). Lower FA and higher MD values were noted in the PWM for both severe MPS II patients, with greater involvement in the untreated patient. The two individuals with attenuated MPS II receiving ERT had near-normal FA and MD. HSCT improved DTI abnormalities without improvement of neurological outcome. Attenuated MPS II post-ERT had slowly progressive somatic disease without neurological involvement. In conclusion, these DTI findings are indicative of abnormal axonal and myelin organization in patients with severe MPS II and lack of major FA and MD in the attenuated phenotypes. doi:10.1016/j.ymgme.2011.11.138
Diagnosis of Mucopolysaccharidosis of a Reference Center Laboratory for Inborn Errors of Metabolism (LEIM) - A Brazilian Experience Marina Rezende, MullerKaren Müller, Ana Maria Martins, Vânia D'Almeida, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil Mucopolysaccharidosis (MPS) are inborn errors of metabolism in which lysosomal enzymatic deficiency leads to glycosaminoglycans accumulation in cell lysosomal compartments. This accumulation is the major responsible for the dysfunction presented in heart, muscles, bones and, sometimes, central nervous system. Depending on the enzyme affected, MPS are subdivided in I, II, III, IV, VI, VII and IX types. The general frequency of this disease is 1:25,000, but there is no consistent data about Brazilian population. The experience of our laboratory with this group of diseases is based on receiving, until now, 385 samples of both genders and age between 0 and 65 years old, with clinical suspicion, from all Brazilian states. The samples received were whole blood tubes and/or dried blood spots, material minimally invasive to collect and of relative easy transport, mainly for the dried blood spots. The analyses are performed by fluorimetric methods in dried blood spots or leukocytes samples. We verified the enzymatic activity of alpha-iduronidase, iduronate 2-sulphatase, galactose-6-sulphatase, arylsulphatase B, which is altered in MPS I, II, IV and VI, respectively. Until now, there were 109 patients with positive results (28.3%), being 44 MPS I (40.3%), 6 MPS II (5.5%), 16 MPS IV (14.7%) and 43 MPS VI (39.5%). Our data suggest that MPS are in an under recognized state and the frequency of these group of lysosomal disease can be higher than expected. Supported by: FAPESP, CNPq, CAPES, AFIP and IGEIM. doi:10.1016/j.ymgme.2011.11.139
Patient Registries to Support Research in Rare Diseases – Experience from the Rare Diseases Clinical Research Network Rachel Richesson a, Denise Shereff a, Rebecca Sutphen a, Heather Guillette a, Kate Paulus a, Peter A. Merkel b, Megan Clowse c, Jennifer Harris a, David Cuthbertson a, Renee Leduc a, Jeffrey P. Krischer a, a University of South Florida College of Medicine, Tampa, FL, USA, bBoston University, Boston, MA, USA, cDuke University, Durham, NC, USA Patient registries are an important component in many diseasespecific research agendas. The number of patient registries is rapidly rising. The lack clear specifications for data collected using patient registries represents a significant data standards gap in an explosively growing application area that is important to both the drug development and patient communities. The Patient Registry Item Specifications and Metadata for Rare Diseases (PRISM) library is a collection of questions used in rare diseases patient registries, designed to support the storage and re-use of questions and answers appropriate for use in a wide variety of registries. The use of the PRISM resource facilitates the efficient development of patient registries, and the standardization of patient registries enables the interoperability of health and research data. The PRISM library is being used as a resource in the registry and research activities of the NIH-funded Rare Diseases Clinical Research Network (RDCRN). In particular, the RDCRN Vasculitis Clinical Research Consortium (VCRC) used PRISM to support the rapid development of an online study exploring the fertility and reproductive outcomes of 452 patients with vasculitis. In addition, PRISM is being used to support extensions of the RDCRN Contact Registry (> 8,100 registrants, > 100 rare diseases). The PRISM resource and the RDCRN Contact Registry model can be leveraged by the RDCRN-affiliated Lysosomal Disease Network to support new partnerships between patient advocacy organizations, researchers, and government sponsors that can increase patient participation in research on lysosomal storage diseases, and ultimately drive the evaluation and availability of new therapeutics. Acknowledgements: The [RD] PRISM Library project is funded by the American Reinvestment and Recovery Act. Support for the [RD] PRISM Library project is administered through the National Library of Medicine. (NLM Grant Number 1RC1LM010455-01, an NIH component, and supported by the Office of Rare Diseases Research. The contents are solely the responsibility of the authors and do not necessarily represent the official views of NLM or ORDR or NIH.) The RDCRN Contact Registry is funded by the National Institute for Neurologic Disease and Stroke (NINDS), (NLM Grant Number 7U54-RR019259-02), a component of the NIH, and supported by the Office of Rare Diseases Research. The contents are solely the responsibility of the authors and do not necessarily represent the official views of NINDS or ORDR or NIH. The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. The Vasculitis Clinical Research Consortium (VCRC) has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. The VCRC is part of the Rare Diseases Clinical Research Network (RDCRN). The VCRC Registry is supported by the Vasculitis Foundation, the Churg-Strauss Syndrome Association, and the PAN Research and Support Network.
doi:10.1016/j.ymgme.2011.11.140