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The lived experience of parents of children with mucopolysaccharidosis (MPS)
Abstracts / Molecular Genetics and Metabolism 120 (2016) S17–S145
Farber disease (Farber lipogranulomatosis, acid ceramidase deficiency) presents in childhood with polyarticular arthritis or joint contractures, subcutaneous nodules, and a hoarse or weak voice due to nodule formation in the larynx. It is caused by mutations in both alleles of the ASAH1 gene, resulting in acid ceramidase deficiency and accumulation of the pro-apoptotic and pro-inflammatory sphingolipid, ceramide. Since 2014 we have established a cohort of 40 patients from 30 countries on 6 continents, which indicates that the phenotypic spectrum is broader than previously thought. A recent report of patients diagnosed at over 40 years of age establishes that peripheral osteolysis can also be caused by ASAH1 mutations, and demonstrates that mild forms of Farber disease may only be diagnosed in adulthood. The prevalence of Farber disease is currently unknown, but it is likely under diagnosed due to lack of awareness of the broad clinical spectrum and of the availability of diagnostic testing. We performed a literature search for Farber disease and pseudonyms, and found 109 cases reported since 1952. We then calculated the percentage of severe phenotypes (defined here as death within the first 4 years of life) in the 78 cases where such information was available (Literature cohort). This data was compared to information reported in 22 patients from our current cohort (Enzyvant cohort), and to data from a case series of 27 patients published in 1982 (Moser cohort). The percentage of severely affected patients in each cohort was as follows: 67% (Literature); 66% (Moser); and 31% (Enzyvant). The number of moderate and attenuated patients is substantially higher in our cohort. This, and the fact that 71% of these patients were initially diagnosed with a form of juvenile idiopathic arthritis, indicates that the incidence and prevalence of Farber disease is likely greater than was previously thought.
doi:10.1016/j.ymgme.2016.11.325
317 Farber disease: design of the first observational and cross-sectional cohort study capturing retrospective and prospective data on the natural history and phenotypic spectrum of patients, including novel methodologies for assessment of disease-specific symptoms Alexander Solyoma, John Mitchellb, Michael Beckc, Boris Hügled, Edward H Schuchmane, aEnzyvant Sciences, New York, NY, United States, bMontreal Children's Hospital, Montreal, QC, Canada, cUniversity of Mainz, Mainz, Germany, dGerman Center for Pediatric Rheumatology, Garmisch-Partenkirchen, Germany, eIchan School of Medicine at Mt. Sinai, New York, NY, United States Farber disease (Farber lipogranulomatosis, acid ceramidase deficiency) is caused by mutations in both alleles of the ASAH1 gene, resulting in deficiency of acid ceramidase and accumulation of the proapoptotic and pro-inflammatory sphingolipid, ceramide. It is considered an ultra-rare disease, with only 109 cases reported in the medical literature since 1952. However, since 2014, we have identified a cohort of 40 patients from 30 countries on 6 continents, which indicates a much broader phenotypic spectrum and potentially higher incidence than previously thought. The information collected from this cohort demonstrates that there are patients diagnosed in late adulthood with slowly-progressive disease, patients for whom years elapse between the appearance of the three typical Farber symptoms (joint disease arthritis and/or contractures, subcutaneous nodules, and hoarseness due to laryngeal involvement), and that intra- and inter-patient variability of symptom severity is great. Enzyvant Sciences is developing recombinant human acid ceramidase enzyme replacement therapy (ERT) for the treatment of Farber disease. As part of the clinical development process, Enzyvant is initiating an observational and crosssectional cohort study to systematically collect data on patients from
S125
around the world, in order to better understand the epidemiology and natural history of the disease, as well as to provide a scientific basis for the selection of endpoints in any future clinical studies. The study design allows for collection of data on deceased patients, in addition to living patients who have and have not undergone hematopoietic stem cell transplantation (HSCT). This study will serve as an opportunity to test a disease-specific data collection instrument, a novel methodology for measuring subcutaneous nodules and their clinical impact, the validity of potential biomarkers, as well as the applicability of patient reported outcome measures and clinical assessments (such as 6 minute walk test) in the heterogeneous Farber disease population. doi:10.1016/j.ymgme.2016.11.326
318 The lived experience of parents of children with mucopolysaccharidosis (MPS) Suja Somanadhana, Philip J Larkinb, aTemple Street Children's University Hospital/University College Dublin, Dublin, Ireland, bUniversity College Dublin, Dublin, Ireland Mucopolysaccharidosis (MPS) is one of the many rare inherited metabolic disorders (IMD) that come under category 3 of life-limiting conditions. The severity of the condition varies according to the specific type, ranging from very mild symptoms to severe, in most cases, multisystemic, restricted growth or mental and physical disabilities. Very little is known about parents’ experience of living and caring for these children, adolescents and young adults with MPS. This study aimed to explore and interpret Irish families’ experiences of living and caring for children with MPS. A qualitative approach, utilising hermeneutic phenomenology was used as a guide for data collection through serial interviewing. A purposively selected sample of parents’ (N=8) attending the Irish National Centre for Inherited Metabolic Disorders was invited to participate. The data was collected over a 17 month period at the threetime point of contact a total of 19 in-depth interviews were completed. The main themes identified during data analysis were described as living with MPS, living with a rare genetic disease, the stigma of a rare condition, MPS as encompassing multiple diseases, unknown future, hospital vs. home, the experience of waiting, a tough road ahead, and things in their day-to-day life with MPS. They spoke of their child’s QoL, their healthy children’s wellbeing, and for some, the impact on their own physical and psychological wellbeing. Parents also spoke about their rite of passage where they move from being the parent of a normal healthy child to being the parent of a child with a life-limiting condition; they predominantly focused on the rite of transition (liminality). It would appear that all the parents in this study were living in a liminal space, experienced a range of uncertainties and made reference to ‘no man’s land’ and ‘future is unknown’ to describe their world. doi:10.1016/j.ymgme.2016.11.327
319 Correction of central nervous system deficits in the mouse model of Hunter syndrome by recombinant iduronate 2-sulfatase crossing the blood-brain barrier Hiroyuki Sonoda, Hideto Morimoto, Yuri Koshimura, Masafumi Kinoshita, JCR Pharmaceuticals Co., Ltd., Kobe, Japan Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an inherited and progressive lysosomal disease. Enzyme replacement
Farber disease (Farber lipogranulomatosis, acid ceramidase deficiency) presents in childhood with polyarticular arthritis or joint contractures, subcutaneous nodules, and a hoarse or weak voice due to nodule formation in the larynx. It is caused by mutations in both alleles of the ASAH1 gene, resulting in acid ceramidase deficiency and accumulation of the pro-apoptotic and pro-inflammatory sphingolipid, ceramide. Since 2014 we have established a cohort of 40 patients from 30 countries on 6 continents, which indicates that the phenotypic spectrum is broader than previously thought. A recent report of patients diagnosed at over 40 years of age establishes that peripheral osteolysis can also be caused by ASAH1 mutations, and demonstrates that mild forms of Farber disease may only be diagnosed in adulthood. The prevalence of Farber disease is currently unknown, but it is likely under diagnosed due to lack of awareness of the broad clinical spectrum and of the availability of diagnostic testing. We performed a literature search for Farber disease and pseudonyms, and found 109 cases reported since 1952. We then calculated the percentage of severe phenotypes (defined here as death within the first 4 years of life) in the 78 cases where such information was available (Literature cohort). This data was compared to information reported in 22 patients from our current cohort (Enzyvant cohort), and to data from a case series of 27 patients published in 1982 (Moser cohort). The percentage of severely affected patients in each cohort was as follows: 67% (Literature); 66% (Moser); and 31% (Enzyvant). The number of moderate and attenuated patients is substantially higher in our cohort. This, and the fact that 71% of these patients were initially diagnosed with a form of juvenile idiopathic arthritis, indicates that the incidence and prevalence of Farber disease is likely greater than was previously thought.
doi:10.1016/j.ymgme.2016.11.325
317 Farber disease: design of the first observational and cross-sectional cohort study capturing retrospective and prospective data on the natural history and phenotypic spectrum of patients, including novel methodologies for assessment of disease-specific symptoms Alexander Solyoma, John Mitchellb, Michael Beckc, Boris Hügled, Edward H Schuchmane, aEnzyvant Sciences, New York, NY, United States, bMontreal Children's Hospital, Montreal, QC, Canada, cUniversity of Mainz, Mainz, Germany, dGerman Center for Pediatric Rheumatology, Garmisch-Partenkirchen, Germany, eIchan School of Medicine at Mt. Sinai, New York, NY, United States Farber disease (Farber lipogranulomatosis, acid ceramidase deficiency) is caused by mutations in both alleles of the ASAH1 gene, resulting in deficiency of acid ceramidase and accumulation of the proapoptotic and pro-inflammatory sphingolipid, ceramide. It is considered an ultra-rare disease, with only 109 cases reported in the medical literature since 1952. However, since 2014, we have identified a cohort of 40 patients from 30 countries on 6 continents, which indicates a much broader phenotypic spectrum and potentially higher incidence than previously thought. The information collected from this cohort demonstrates that there are patients diagnosed in late adulthood with slowly-progressive disease, patients for whom years elapse between the appearance of the three typical Farber symptoms (joint disease arthritis and/or contractures, subcutaneous nodules, and hoarseness due to laryngeal involvement), and that intra- and inter-patient variability of symptom severity is great. Enzyvant Sciences is developing recombinant human acid ceramidase enzyme replacement therapy (ERT) for the treatment of Farber disease. As part of the clinical development process, Enzyvant is initiating an observational and crosssectional cohort study to systematically collect data on patients from
S125
around the world, in order to better understand the epidemiology and natural history of the disease, as well as to provide a scientific basis for the selection of endpoints in any future clinical studies. The study design allows for collection of data on deceased patients, in addition to living patients who have and have not undergone hematopoietic stem cell transplantation (HSCT). This study will serve as an opportunity to test a disease-specific data collection instrument, a novel methodology for measuring subcutaneous nodules and their clinical impact, the validity of potential biomarkers, as well as the applicability of patient reported outcome measures and clinical assessments (such as 6 minute walk test) in the heterogeneous Farber disease population. doi:10.1016/j.ymgme.2016.11.326
318 The lived experience of parents of children with mucopolysaccharidosis (MPS) Suja Somanadhana, Philip J Larkinb, aTemple Street Children's University Hospital/University College Dublin, Dublin, Ireland, bUniversity College Dublin, Dublin, Ireland Mucopolysaccharidosis (MPS) is one of the many rare inherited metabolic disorders (IMD) that come under category 3 of life-limiting conditions. The severity of the condition varies according to the specific type, ranging from very mild symptoms to severe, in most cases, multisystemic, restricted growth or mental and physical disabilities. Very little is known about parents’ experience of living and caring for these children, adolescents and young adults with MPS. This study aimed to explore and interpret Irish families’ experiences of living and caring for children with MPS. A qualitative approach, utilising hermeneutic phenomenology was used as a guide for data collection through serial interviewing. A purposively selected sample of parents’ (N=8) attending the Irish National Centre for Inherited Metabolic Disorders was invited to participate. The data was collected over a 17 month period at the threetime point of contact a total of 19 in-depth interviews were completed. The main themes identified during data analysis were described as living with MPS, living with a rare genetic disease, the stigma of a rare condition, MPS as encompassing multiple diseases, unknown future, hospital vs. home, the experience of waiting, a tough road ahead, and things in their day-to-day life with MPS. They spoke of their child’s QoL, their healthy children’s wellbeing, and for some, the impact on their own physical and psychological wellbeing. Parents also spoke about their rite of passage where they move from being the parent of a normal healthy child to being the parent of a child with a life-limiting condition; they predominantly focused on the rite of transition (liminality). It would appear that all the parents in this study were living in a liminal space, experienced a range of uncertainties and made reference to ‘no man’s land’ and ‘future is unknown’ to describe their world. doi:10.1016/j.ymgme.2016.11.327
319 Correction of central nervous system deficits in the mouse model of Hunter syndrome by recombinant iduronate 2-sulfatase crossing the blood-brain barrier Hiroyuki Sonoda, Hideto Morimoto, Yuri Koshimura, Masafumi Kinoshita, JCR Pharmaceuticals Co., Ltd., Kobe, Japan Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an inherited and progressive lysosomal disease. Enzyme replacement