- Email: [email protected]
Significant abdominal and acute pain improvements in young patients with Fabry disease initiated on agalsidase beta treatment before age 30: A Fabry registry analysis
S74
Abstracts / Molecular Genetics and Metabolism 126 (2019) S17–S156
interpretation of the results. Funding (Fabry Registry, abstract): Sanofi Genzyme.
females after sustained agalsidase beta treatment. Funding (Fabry Registry, abstract): Sanofi Genzyme.
doi:10.1016/j.ymgme.2018.12.177
doi:10.1016/j.ymgme.2018.12.178
162 Significant abdominal and acute pain improvements in young patients with Fabry disease initiated on agalsidase beta treatment before age 30: A Fabry registry analysis
163 Bone/joint abnormalities in children/adolescents: A screening protocol for mucopolysaccharidosis
Robert J. Hopkina, Gustavo H. Cabrerab, John L. Jefferiesc, Eva Brandd, Ulla Feldt-Rasmussene, Dominique P. Germainf, Nathalie Guffong, Ana Jovanovich, Ilkka Kantolai, Amel Karaaj, Ana M. Martinsk, William R. Wilcoxl, Meng Yangm, Han-Wook Yoon, Michael Mauero, aCincinnati Children's Hospital Medical Center, University of Cincinnati College Medicine, Cincinnati, OH, United States, bCentro Médico Santa María de la Salud, Buenos Aires, Argentina, cUniversity of Tennessee Health Science Center, Methodist University of Tennessee, Memphis, TN, United States, dUniversity Hospital Münster, Münster, Germany, eRigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, fUniversity of Versailles, Paris-Saclay University, Montigny, France, gFemme Mère Enfant Hospital, Lyon, France, hSalford Royal NHS Foundation Trust, Salford, United Kingdom, iTurku University Hospital, Turku, Finland, j Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, kFederal University of Sao Paulo, Sao Paulo, Brazil, l Emory University School of Medicine, Atlanta, GA, United States, m Sanofi Genzyme, Cambridge, MA, United States, nUniversity of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea, o University of Minnesota, Minneapolis, MN, United States Fabry disease (FD) is a progressive X-linked disorder from deficiency of α-galactosidase. Gastrointestinal symptoms, neuropathic pain, and attacks of excruciating pain are among the earliest symptoms. This Fabry Registry (NCT00196742) analysis assessed changes in symptom reports from male and female patients on agalsidase beta with age at first treatment of 5-30 years. GLA variants were classic or unclassified (fabry-database.org), which shared similar clinical features. We compared patient-reported binary responses (yes [present]/no [not present]) for abdominal pain, diarrhea, and peripheral and acute pain between baseline and last follow-up ≥0.5 or ≥2.5 years on treatment separately. Ages at first treatment and follow-up durations were expressed as group medians. Of the early symptoms, peripheral pain was most frequently reported at baseline by the vast majority of the patients. Acute pain was least frequently reported. Compared to baseline, significantly fewer males with ≥0.5 years follow-up reported acute pain after 2.1-year follow-up (17/78 [21.8%] vs. 7/78 [9%], P=0.012, age at first treatment 17.3 years). Data was more limited for patients with ≥2.5 year responses. Among males, the significant decrease in acute pain reports remained after median 4.2-year follow-up (baseline 11/31 [35.3%], follow-up 1/31 [3.2%], P=0.002). Additionally, much fewer males and females reported abdominal pain after median 4.2- and 3.6-year follow-ups, respectively, compared to baseline (males: 21/29 [72.4%] vs. 10/29 [34.5%], P=0.002 females: 12/18 [66.7%] vs. 6/18 [33.3%], P=0.034, ages at first treatment were 21.3 and 22.4 years, respectively). There were no significant changes in yes/no responses for diarrhea or peripheral pain. In conclusion, in young FD patients a reduction in reported acute pain in treated males was sustained over the duration of follow-up. Furthermore, there were fewer reports of abdominal pain in both males and
Dafne D.G. Horovitza, Anneliese L. Bartha, Pedro H. Barros Mendesb, Mariana Q.G. Gonzagaa, Yuri L. Chistéb, Rommel B. Medeirosb, Maria L. Oliveirac, Fernanda B. Scalcoc, aNational Institute of Women, Children and Adolescents Health Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil, bInstituto Nacional de Traumato Ortopedia - Into, Rio de Janeiro, Brazil, cLABEIM, Rio de Janeiro, Brazil Mucopolysaccharidoses (MPS) are under-diagnosed, especially milder forms. A screening protocol was tested at the National Institute of Orthopedics in Rio de Janeiro - Brazil. Patients were selected from Pediatric Orthopedics, Spine and Hand clinics. Inclusion criteria were age under 18, suspected Legg-Calve-Perthes disease, scoliosis, kyphosis, genu valgum, trigger finger, carpal tunnel syndrome, atypical epiphyseal dysplasia and short stature, associated or not to dysostosis exclusion criteria were confirmed diagnosis of other genetic bone disease and chronic disorders with bone abnormalities. Patients were clinically evaluated to identify other signs / symptoms of MPS, with information on infections, surgeries and other morbidities, other specialists seen and family history. Selected patients underwent hand/ wrist and lateral lumbar spine X-rays and provided urine sample for GAG analyses. Clinical forms, X-rays and urinary results were reviewed by a genetics team familiar with MPS. Patients with X-ray abnormalities suggestive of MPS and/or abnormal urinary analysis were selected for re-evaluation by genetics and blood collection for enzyme activity studies. If necessary, additional exams (complete skeletal X-rays, echocardiogram or others) were ordered. From November 2015 to October 2017, 1119 pediatric patients were evaluated and 55 selected for X-rays and urinary GAG analyses. Two did not complete the exams and were excluded. In the remaining 53, MPS was ruled out in 51 after comprehensive clinical evaluation, more complete imaging and enzyme activity studies in selected cases. Two patients with short stature, genu valgum, oar shaped ribs, abnormal spine and metacarpals had normal urinary GAGs enzyme activity studies will be ordered. So far, no MPS diagnosis was confirmed. We diagnosed a spondiloepiphyseal dysplasia and an epiphyseal dysplasia. Despite not having MPS confirmed, we believe the protocol can be effective, although In future studies isolated scoliosis will no longer be an inclusion criterion. Acknowledgements: Biomarin - financial support Rede MPS Brasil enzyme studies.
doi:10.1016/j.ymgme.2018.12.179
164 Enzyme replacement therapy in mucopolysaccharidosis type II with alternative dosing 1mg/kg idursulfase in every other week infusions Dafne D. Horovitza, Anneliese L. Bartha, Carolina F. Souzab, Sueli G. Canossac, Marco A. Curiatic, Sandra O. Kyosenc, Maria L. Oliveirad,
Abstracts / Molecular Genetics and Metabolism 126 (2019) S17–S156
interpretation of the results. Funding (Fabry Registry, abstract): Sanofi Genzyme.
females after sustained agalsidase beta treatment. Funding (Fabry Registry, abstract): Sanofi Genzyme.
doi:10.1016/j.ymgme.2018.12.177
doi:10.1016/j.ymgme.2018.12.178
162 Significant abdominal and acute pain improvements in young patients with Fabry disease initiated on agalsidase beta treatment before age 30: A Fabry registry analysis
163 Bone/joint abnormalities in children/adolescents: A screening protocol for mucopolysaccharidosis
Robert J. Hopkina, Gustavo H. Cabrerab, John L. Jefferiesc, Eva Brandd, Ulla Feldt-Rasmussene, Dominique P. Germainf, Nathalie Guffong, Ana Jovanovich, Ilkka Kantolai, Amel Karaaj, Ana M. Martinsk, William R. Wilcoxl, Meng Yangm, Han-Wook Yoon, Michael Mauero, aCincinnati Children's Hospital Medical Center, University of Cincinnati College Medicine, Cincinnati, OH, United States, bCentro Médico Santa María de la Salud, Buenos Aires, Argentina, cUniversity of Tennessee Health Science Center, Methodist University of Tennessee, Memphis, TN, United States, dUniversity Hospital Münster, Münster, Germany, eRigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, fUniversity of Versailles, Paris-Saclay University, Montigny, France, gFemme Mère Enfant Hospital, Lyon, France, hSalford Royal NHS Foundation Trust, Salford, United Kingdom, iTurku University Hospital, Turku, Finland, j Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, kFederal University of Sao Paulo, Sao Paulo, Brazil, l Emory University School of Medicine, Atlanta, GA, United States, m Sanofi Genzyme, Cambridge, MA, United States, nUniversity of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea, o University of Minnesota, Minneapolis, MN, United States Fabry disease (FD) is a progressive X-linked disorder from deficiency of α-galactosidase. Gastrointestinal symptoms, neuropathic pain, and attacks of excruciating pain are among the earliest symptoms. This Fabry Registry (NCT00196742) analysis assessed changes in symptom reports from male and female patients on agalsidase beta with age at first treatment of 5-30 years. GLA variants were classic or unclassified (fabry-database.org), which shared similar clinical features. We compared patient-reported binary responses (yes [present]/no [not present]) for abdominal pain, diarrhea, and peripheral and acute pain between baseline and last follow-up ≥0.5 or ≥2.5 years on treatment separately. Ages at first treatment and follow-up durations were expressed as group medians. Of the early symptoms, peripheral pain was most frequently reported at baseline by the vast majority of the patients. Acute pain was least frequently reported. Compared to baseline, significantly fewer males with ≥0.5 years follow-up reported acute pain after 2.1-year follow-up (17/78 [21.8%] vs. 7/78 [9%], P=0.012, age at first treatment 17.3 years). Data was more limited for patients with ≥2.5 year responses. Among males, the significant decrease in acute pain reports remained after median 4.2-year follow-up (baseline 11/31 [35.3%], follow-up 1/31 [3.2%], P=0.002). Additionally, much fewer males and females reported abdominal pain after median 4.2- and 3.6-year follow-ups, respectively, compared to baseline (males: 21/29 [72.4%] vs. 10/29 [34.5%], P=0.002 females: 12/18 [66.7%] vs. 6/18 [33.3%], P=0.034, ages at first treatment were 21.3 and 22.4 years, respectively). There were no significant changes in yes/no responses for diarrhea or peripheral pain. In conclusion, in young FD patients a reduction in reported acute pain in treated males was sustained over the duration of follow-up. Furthermore, there were fewer reports of abdominal pain in both males and
Dafne D.G. Horovitza, Anneliese L. Bartha, Pedro H. Barros Mendesb, Mariana Q.G. Gonzagaa, Yuri L. Chistéb, Rommel B. Medeirosb, Maria L. Oliveirac, Fernanda B. Scalcoc, aNational Institute of Women, Children and Adolescents Health Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil, bInstituto Nacional de Traumato Ortopedia - Into, Rio de Janeiro, Brazil, cLABEIM, Rio de Janeiro, Brazil Mucopolysaccharidoses (MPS) are under-diagnosed, especially milder forms. A screening protocol was tested at the National Institute of Orthopedics in Rio de Janeiro - Brazil. Patients were selected from Pediatric Orthopedics, Spine and Hand clinics. Inclusion criteria were age under 18, suspected Legg-Calve-Perthes disease, scoliosis, kyphosis, genu valgum, trigger finger, carpal tunnel syndrome, atypical epiphyseal dysplasia and short stature, associated or not to dysostosis exclusion criteria were confirmed diagnosis of other genetic bone disease and chronic disorders with bone abnormalities. Patients were clinically evaluated to identify other signs / symptoms of MPS, with information on infections, surgeries and other morbidities, other specialists seen and family history. Selected patients underwent hand/ wrist and lateral lumbar spine X-rays and provided urine sample for GAG analyses. Clinical forms, X-rays and urinary results were reviewed by a genetics team familiar with MPS. Patients with X-ray abnormalities suggestive of MPS and/or abnormal urinary analysis were selected for re-evaluation by genetics and blood collection for enzyme activity studies. If necessary, additional exams (complete skeletal X-rays, echocardiogram or others) were ordered. From November 2015 to October 2017, 1119 pediatric patients were evaluated and 55 selected for X-rays and urinary GAG analyses. Two did not complete the exams and were excluded. In the remaining 53, MPS was ruled out in 51 after comprehensive clinical evaluation, more complete imaging and enzyme activity studies in selected cases. Two patients with short stature, genu valgum, oar shaped ribs, abnormal spine and metacarpals had normal urinary GAGs enzyme activity studies will be ordered. So far, no MPS diagnosis was confirmed. We diagnosed a spondiloepiphyseal dysplasia and an epiphyseal dysplasia. Despite not having MPS confirmed, we believe the protocol can be effective, although In future studies isolated scoliosis will no longer be an inclusion criterion. Acknowledgements: Biomarin - financial support Rede MPS Brasil enzyme studies.
doi:10.1016/j.ymgme.2018.12.179
164 Enzyme replacement therapy in mucopolysaccharidosis type II with alternative dosing 1mg/kg idursulfase in every other week infusions Dafne D. Horovitza, Anneliese L. Bartha, Carolina F. Souzab, Sueli G. Canossac, Marco A. Curiatic, Sandra O. Kyosenc, Maria L. Oliveirad,