- Email: [email protected]
Adult-onset Niemann-Pick disease type C patients treated with miglustat, the Finnish experience
Abstracts / Molecular Genetics and Metabolism 117 (2016) S14–S124
131 Proteomic analysis of urine reveals potential markers for CLN2 Batten disease Wendy E. Heywooda, Ivan Doykova, Ernestas Sirkaa, Robert Claytona, Barbara Csányib, Maureen Clearyb, Emma Footittb, Anupam Chakrapanib, Lara Abulhoulb, Stephanie Grunewaldb, Sara Molea, Paul Gissenb, Kevin Millsa, aUCL, London, United Kingdom, bGreat Ormond Street Hospital, London, United Kingdom
S57
case. The younger sister did not have pre-treatment dysphagia, but her mother had noticed lenghtening of the time the patient used for eating. Problems in drinking liquids were first observed when the patient had been 15 months on miglustat. That time, her swallowing speed was 1,39 ml/s and she got 2 points on PAS. According to our experience, miglustat is not able to prevent the progression of dysphagia, especially if the patients already have severe symptoms at the beginning of the treatment. doi:10.1016/j.ymgme.2015.12.290
The neuronal ceroid lipofuscinoses or Batten disease (BD) are the most common inherited, neurodegenerative lysosomal diseases and one of the most common causes of childhood dementia. BD classification is based on the affected gene and the age of onset of which CLN2 is one such affected gene. Characteristically, many cell types from affected patients accumulate an autofluorescent storage material in their lysosomes. Currently, diagnosis is based on clinical signs, enzyme activity measurements and genetic testing. Arriving at the correct diagnosis can be time-consuming and difficult, especially for those types that are not caused by readily detectable enzyme defects. Of recent new treatments for BD are being tested and developed and hence there is a need to find a more effective method that can be used to diagnose and monitor potential treatments for BD. Label free urinary proteomic analyses was performed on 3 Batten disease patients (mild and severely affected CLN2 disease) versus 4 age-matched control urines. Using this technology, we were able to identify N1500 proteins in 2 ml of urine and demonstrate 48 proteins that showed a N2-fold change in concentration compared to agematched controls. Of these 48 proteins, approximately 50% have been observed in other lysosomal diseases (both mucopolysaccharidoses (MPS) and the glycosphingolipidoses) in keeping with BD as a lysosomal disease. The remaining 50% have never been observed in any omic analyses we have performed previously, suggesting that they are specific to BD or even to CLN2 disease. Pathway analyses of the data indicate changes in the metabolic pathways involved in MAPK regulation/DNA helicase regulation, lamellar body and lysosomal function including glucosaminoglycan (GAG) homeostasis and peptidase activity. These proteins may potentially reflect ongoing disease processes affected in CLN2 battens disease and potentially be used as markers for monitoring of future treatment
doi:10.1016/j.ymgme.2015.12.289
132 Adult-onset Niemann-Pick disease type C patients treated with miglustat, the Finnish experience Aki Hietaharju, Tanja Makkonen, Tampere University Hospital, Tampere, Finland Two sisters were diagnosed with Niemann-Pick disease type C in 2013. Both of them had suffered from progressive neurological symptoms more than 4 years. Miglustat treatment was started after confirmation of the diagnosis. The effect of the treatment on dysphagia was evaluated by using the 100 ml water swallow test (WST), Rosenbek’s 8-point penetration-aspiration scale (PAS), videofluorography (VFG) and fiberoptic endoscopic evaluation (FEES). The older sister had already difficulties with swallowing at the time of diagnosis. Her pre-treatment swallowing speed was 1,54 ml/s. After 24 months of treatment, her swallowing speed was 0.27 ml/s. Risk for aspiration had also increased from 2 points to 4-5 points on PAS. Slowness of the oral phase, associated with progressive cognitive impairment, has been the most significant cause of dysphagia in her
133 Impact of social media use in Fabry and Gaucher diseases Amanda Hodgkins, Emily Lisi, Nadia Ali, Emory University School of Medicine, Decatur, GA, United States Fabry disease (FD) and Gaucher disease (GD) are lysosomal (LD) caused by enzyme deficiencies leading to multi-organ system damage. While FD treatment is only available via enzyme replacement therapy (ERT), GD treatment consists of ERT or pill. Since people with chronic diseases are increasingly using online social networks (OSN) to connect and discuss health concerns, this study explores OSN use among people with FD and GD. In-depth interviews were conducted with 21 individuals, ten with FD and eleven with GD. Information about OSN support group use, positive/negative experiences, and suggestions for other patients and healthcare providers was collected and analyzed using Grounded Theory. Three independent raters coded the data for qualitative themes. Cohen’s kappa interrater reliability was .80. Preliminary analysis suggests three distinct types of OSN users in FD and GD populations: givers, receivers and voyeurs. Givers expressed themes of altruism and validation, as well as foreshadowing and secondary adversity (i.e. the concept of feeling stressed by exposure to other people’s stress). Receivers expressed themes of social support, normalization, validation and anticipatory guidance. Voyeurs also experienced normalization and validation but tend only to read OSN posts rather than posting themselves. Motivators for OSN use include increased disease severity, isolation, and community formation. Deterrents include greater support outside of OSN, privacy concerns, and group negativity. Individuals N40 years were likely to have greater disease severity, be OSN givers/receivers, and attribute greater significance to OSN support groups. Individuals b39 years were more likely to use OSN in general but less likely to use OSN support groups. Due to receiving treatment earlier, younger individuals may perceive less impact of the disease on their life and thus seek OSN support groups less frequently. Overall, OSN use among people with FD/GD was associated with age, disease severity, and desire for support and connectivity. doi:10.1016/j.ymgme.2015.12.291
134 Improvement of Fabry disease related gastrointestinal symptoms in a significant proportion of female patients treated with agalsidase beta Robert Hopkina, Ulla Feldt-Rasmussenb, Ana Maria Martinsc, Alberto Ortizd, Frank Weidemanne, Roberta Lemayf, William R. Wilcoxg, a Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, b Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, c Universidade Federal de São Paulo, São Paulo, Brazil, dUniversidad Autonoma de Madrid, Madrid, Spain, eKatharinen-Hospital Unna, Unna,
131 Proteomic analysis of urine reveals potential markers for CLN2 Batten disease Wendy E. Heywooda, Ivan Doykova, Ernestas Sirkaa, Robert Claytona, Barbara Csányib, Maureen Clearyb, Emma Footittb, Anupam Chakrapanib, Lara Abulhoulb, Stephanie Grunewaldb, Sara Molea, Paul Gissenb, Kevin Millsa, aUCL, London, United Kingdom, bGreat Ormond Street Hospital, London, United Kingdom
S57
case. The younger sister did not have pre-treatment dysphagia, but her mother had noticed lenghtening of the time the patient used for eating. Problems in drinking liquids were first observed when the patient had been 15 months on miglustat. That time, her swallowing speed was 1,39 ml/s and she got 2 points on PAS. According to our experience, miglustat is not able to prevent the progression of dysphagia, especially if the patients already have severe symptoms at the beginning of the treatment. doi:10.1016/j.ymgme.2015.12.290
The neuronal ceroid lipofuscinoses or Batten disease (BD) are the most common inherited, neurodegenerative lysosomal diseases and one of the most common causes of childhood dementia. BD classification is based on the affected gene and the age of onset of which CLN2 is one such affected gene. Characteristically, many cell types from affected patients accumulate an autofluorescent storage material in their lysosomes. Currently, diagnosis is based on clinical signs, enzyme activity measurements and genetic testing. Arriving at the correct diagnosis can be time-consuming and difficult, especially for those types that are not caused by readily detectable enzyme defects. Of recent new treatments for BD are being tested and developed and hence there is a need to find a more effective method that can be used to diagnose and monitor potential treatments for BD. Label free urinary proteomic analyses was performed on 3 Batten disease patients (mild and severely affected CLN2 disease) versus 4 age-matched control urines. Using this technology, we were able to identify N1500 proteins in 2 ml of urine and demonstrate 48 proteins that showed a N2-fold change in concentration compared to agematched controls. Of these 48 proteins, approximately 50% have been observed in other lysosomal diseases (both mucopolysaccharidoses (MPS) and the glycosphingolipidoses) in keeping with BD as a lysosomal disease. The remaining 50% have never been observed in any omic analyses we have performed previously, suggesting that they are specific to BD or even to CLN2 disease. Pathway analyses of the data indicate changes in the metabolic pathways involved in MAPK regulation/DNA helicase regulation, lamellar body and lysosomal function including glucosaminoglycan (GAG) homeostasis and peptidase activity. These proteins may potentially reflect ongoing disease processes affected in CLN2 battens disease and potentially be used as markers for monitoring of future treatment
doi:10.1016/j.ymgme.2015.12.289
132 Adult-onset Niemann-Pick disease type C patients treated with miglustat, the Finnish experience Aki Hietaharju, Tanja Makkonen, Tampere University Hospital, Tampere, Finland Two sisters were diagnosed with Niemann-Pick disease type C in 2013. Both of them had suffered from progressive neurological symptoms more than 4 years. Miglustat treatment was started after confirmation of the diagnosis. The effect of the treatment on dysphagia was evaluated by using the 100 ml water swallow test (WST), Rosenbek’s 8-point penetration-aspiration scale (PAS), videofluorography (VFG) and fiberoptic endoscopic evaluation (FEES). The older sister had already difficulties with swallowing at the time of diagnosis. Her pre-treatment swallowing speed was 1,54 ml/s. After 24 months of treatment, her swallowing speed was 0.27 ml/s. Risk for aspiration had also increased from 2 points to 4-5 points on PAS. Slowness of the oral phase, associated with progressive cognitive impairment, has been the most significant cause of dysphagia in her
133 Impact of social media use in Fabry and Gaucher diseases Amanda Hodgkins, Emily Lisi, Nadia Ali, Emory University School of Medicine, Decatur, GA, United States Fabry disease (FD) and Gaucher disease (GD) are lysosomal (LD) caused by enzyme deficiencies leading to multi-organ system damage. While FD treatment is only available via enzyme replacement therapy (ERT), GD treatment consists of ERT or pill. Since people with chronic diseases are increasingly using online social networks (OSN) to connect and discuss health concerns, this study explores OSN use among people with FD and GD. In-depth interviews were conducted with 21 individuals, ten with FD and eleven with GD. Information about OSN support group use, positive/negative experiences, and suggestions for other patients and healthcare providers was collected and analyzed using Grounded Theory. Three independent raters coded the data for qualitative themes. Cohen’s kappa interrater reliability was .80. Preliminary analysis suggests three distinct types of OSN users in FD and GD populations: givers, receivers and voyeurs. Givers expressed themes of altruism and validation, as well as foreshadowing and secondary adversity (i.e. the concept of feeling stressed by exposure to other people’s stress). Receivers expressed themes of social support, normalization, validation and anticipatory guidance. Voyeurs also experienced normalization and validation but tend only to read OSN posts rather than posting themselves. Motivators for OSN use include increased disease severity, isolation, and community formation. Deterrents include greater support outside of OSN, privacy concerns, and group negativity. Individuals N40 years were likely to have greater disease severity, be OSN givers/receivers, and attribute greater significance to OSN support groups. Individuals b39 years were more likely to use OSN in general but less likely to use OSN support groups. Due to receiving treatment earlier, younger individuals may perceive less impact of the disease on their life and thus seek OSN support groups less frequently. Overall, OSN use among people with FD/GD was associated with age, disease severity, and desire for support and connectivity. doi:10.1016/j.ymgme.2015.12.291
134 Improvement of Fabry disease related gastrointestinal symptoms in a significant proportion of female patients treated with agalsidase beta Robert Hopkina, Ulla Feldt-Rasmussenb, Ana Maria Martinsc, Alberto Ortizd, Frank Weidemanne, Roberta Lemayf, William R. Wilcoxg, a Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, b Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, c Universidade Federal de São Paulo, São Paulo, Brazil, dUniversidad Autonoma de Madrid, Madrid, Spain, eKatharinen-Hospital Unna, Unna,