Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype
Background: Fabry disease is an inherited disorder of glycolipid metabolism with progressive involvement of multiple organs, including the gastrointestinal tract, in classically affected male patients. Clinical presentations in males with later-onset Fabry phenotypes are more heterogeneous and large...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426920301166 |
| _version_ | 1828920998785712128 |
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| author | Robert J. Hopkin Ulla Feldt-Rasmussen Dominique P. Germain Ana Jovanovic Ana Maria Martins Kathleen Nicholls Alberto Ortiz Juan Politei Elvira Ponce Carmen Varas Frank Weidemann Meng Yang William R. Wilcox |
| author_facet | Robert J. Hopkin Ulla Feldt-Rasmussen Dominique P. Germain Ana Jovanovic Ana Maria Martins Kathleen Nicholls Alberto Ortiz Juan Politei Elvira Ponce Carmen Varas Frank Weidemann Meng Yang William R. Wilcox |
| author_sort | Robert J. Hopkin |
| collection | DOAJ |
| description | Background: Fabry disease is an inherited disorder of glycolipid metabolism with progressive involvement of multiple organs, including the gastrointestinal tract, in classically affected male patients. Clinical presentations in males with later-onset Fabry phenotypes are more heterogeneous and largely dependent on the level of residual α-galactosidase A activity. Methods: We assessed agalsidase beta treatment outcomes of gastrointestinal symptoms in adult males with classic or later-onset Fabry disease. Self-reports of abdominal pain and diarrhea (‘present’/’not present’ since previous assessment) at last clinical visit (≥0.5 year of follow-up) were compared with treatment-baseline. Results: Classic male patients were considerably younger at first treatment than the fewer males with later-onset phenotypes (36 vs. ~47 years) and reported gastrointestinal symptoms more frequently at baseline (abdominal pain: 56% vs. 13%; diarrhea: 57% vs. 23%). As compared with baseline, significantly fewer classic patients reported abdominal pain after a median of 4.7 years of treatment (N = 171, 56% vs. 41%, P < 0.001). Moreover, significantly fewer patients reported diarrhea after 5.5 years of follow-up (N = 169, 57% vs. 47%, P < 0.05). Among the males with later-onset phenotypes, albeit statistically non-significant, abdominal pain reports reduced after a median of 4.2 years (N = 48, 13% vs. 4%) and diarrhea reports reduced after a median of 4.4 years of treatment (N = 47, 23% vs. 13%). Conclusions: Sustained treatment with agalsidase beta was associated with improvement in abdominal pain and diarrhea in a significant proportion of classic male Fabry patients. Males with later-onset phenotypes reported gastrointestinal symptoms much less frequently at baseline as compared with classic patients, and non-significant reductions were observed. |
| first_indexed | 2024-12-13T21:56:29Z |
| format | Article |
| id | doaj.art-539b308254b24c07ac41d8b8ceeb4b74 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-13T21:56:29Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
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| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-539b308254b24c07ac41d8b8ceeb4b742022-12-21T23:30:08ZengElsevierMolecular Genetics and Metabolism Reports2214-42692020-12-0125100670Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotypeRobert J. Hopkin0Ulla Feldt-Rasmussen1Dominique P. Germain2Ana Jovanovic3Ana Maria Martins4Kathleen Nicholls5Alberto Ortiz6Juan Politei7Elvira Ponce8Carmen Varas9Frank Weidemann10Meng Yang11William R. Wilcox12Division of Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Corresponding author at: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., ML 4006, Cincinnati, OH 45229-3039, USA.Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkFrench Referral Centre for Fabry disease, Division of Medical Genetics, Paris Saclay University, Garches, FranceThe Mark Holland Unit, Department of Endocrinology and Metabolic Medicine, Salford Royal NHS Foundation Trust, Salford, UKReference Center for Inborn Errors of Metabolism, Federal University of São Paulo, São Paulo, BrazilDepartment of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, AustraliaUnidad de Dialisis, IIS-Fundación Jiménez Díaz, UAM, IRSIN and REDINREN, Madrid, SpainNeurology Department, Fundación para el Estudio de las Enfermedades Neurometabólicas (FESEN), Buenos Aires, ArgentinaGlobal Medical Affairs Rare Diseases, Sanofi Genzyme, Cambridge, MA, USAFabry Disease Multidisciplinary Team, Hospital San Pablo de Coquimbo, Coquimbo, ChileMedical Clinic I, Klinikum Vest, Knappschaftskrankenhaus, Recklinghausen, GermanyEpidemiology & Biostatistics, Sanofi Genzyme, Cambridge, MA, USADepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USABackground: Fabry disease is an inherited disorder of glycolipid metabolism with progressive involvement of multiple organs, including the gastrointestinal tract, in classically affected male patients. Clinical presentations in males with later-onset Fabry phenotypes are more heterogeneous and largely dependent on the level of residual α-galactosidase A activity. Methods: We assessed agalsidase beta treatment outcomes of gastrointestinal symptoms in adult males with classic or later-onset Fabry disease. Self-reports of abdominal pain and diarrhea (‘present’/’not present’ since previous assessment) at last clinical visit (≥0.5 year of follow-up) were compared with treatment-baseline. Results: Classic male patients were considerably younger at first treatment than the fewer males with later-onset phenotypes (36 vs. ~47 years) and reported gastrointestinal symptoms more frequently at baseline (abdominal pain: 56% vs. 13%; diarrhea: 57% vs. 23%). As compared with baseline, significantly fewer classic patients reported abdominal pain after a median of 4.7 years of treatment (N = 171, 56% vs. 41%, P < 0.001). Moreover, significantly fewer patients reported diarrhea after 5.5 years of follow-up (N = 169, 57% vs. 47%, P < 0.05). Among the males with later-onset phenotypes, albeit statistically non-significant, abdominal pain reports reduced after a median of 4.2 years (N = 48, 13% vs. 4%) and diarrhea reports reduced after a median of 4.4 years of treatment (N = 47, 23% vs. 13%). Conclusions: Sustained treatment with agalsidase beta was associated with improvement in abdominal pain and diarrhea in a significant proportion of classic male Fabry patients. Males with later-onset phenotypes reported gastrointestinal symptoms much less frequently at baseline as compared with classic patients, and non-significant reductions were observed.http://www.sciencedirect.com/science/article/pii/S2214426920301166Abdominal painAgalsidase betaDiarrheaFabry diseaseFabry RegistryPhenotypes |
| spellingShingle | Robert J. Hopkin Ulla Feldt-Rasmussen Dominique P. Germain Ana Jovanovic Ana Maria Martins Kathleen Nicholls Alberto Ortiz Juan Politei Elvira Ponce Carmen Varas Frank Weidemann Meng Yang William R. Wilcox Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype Molecular Genetics and Metabolism Reports Abdominal pain Agalsidase beta Diarrhea Fabry disease Fabry Registry Phenotypes |
| title | Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype |
| title_full | Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype |
| title_fullStr | Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype |
| title_full_unstemmed | Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype |
| title_short | Improvement of gastrointestinal symptoms in a significant proportion of male patients with classic Fabry disease treated with agalsidase beta: A Fabry Registry analysis stratified by phenotype |
| title_sort | improvement of gastrointestinal symptoms in a significant proportion of male patients with classic fabry disease treated with agalsidase beta a fabry registry analysis stratified by phenotype |
| topic | Abdominal pain Agalsidase beta Diarrhea Fabry disease Fabry Registry Phenotypes |
| url | http://www.sciencedirect.com/science/article/pii/S2214426920301166 |
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