The clinical profiles of female patients with Fabry disease in Latin America: A Fabry Registry analysis of natural history data from 169 patients based on enzyme replacement therapy status.

Autor: Martins AM; Reference Center for Inborn Errors of Metabolism Federal University of São Paulo São Paulo SP Brazil., Cabrera G; Centro Médico Santa María de la Salud Buenos Aires Argentina., Molt F; Departamento de Clínicas, Facultad de Medicina Universidad Católica del Norte Coquimbo Chile.; Fabry Disease Multidisciplinary Team Hospital San Pablo de Coquimbo Coquimbo Chile., Suárez-Obando F; Instituto de Genética Humana, Facultad de Medicina, Hospital Universitario San Ignacio Pontificia Universidad Javeriana Bogota Colombia., Valdés RA; National Dialysis Coordinator of Social Security of Panama Panama City Panama., Varas C; Fabry Disease Multidisciplinary Team Hospital San Pablo de Coquimbo Coquimbo Chile., Yang M; Sanofi Genzyme Cambridge Massachusetts., Politei JM; Department of Neurology Fundación Para el Estudio de Enfermedades Neurometabólicas (FESEN) Buenos Aires Argentina.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2019 Aug 05; Vol. 49 (1), pp. 107-117. Date of Electronic Publication: 2019 Aug 05 (Print Publication: 2019).
DOI: 10.1002/jmd2.12071
Abstrakt: Background: Fabry disease is an X-linked lysosomal storage disorder with heterogeneous clinical expression in female patients ranging from asymptomatic to severe clinical presentations as in classic males. We assessed clinical profiles and compared natural history data of female patients eventually initiated on enzyme replacement therapy ("ERT-recipients") with those remaining untreated ("ERT-naïve").
Methods: We analyzed Fabry Registry data from 93 ERT-recipients, collected prior to ERT initiation, and 76 ERT-naïve females with classic or unclassified phenotypes from four Latin American countries and evaluated Fabry symptoms, interventricular septum thickness, left ventricular posterior wall thickness, estimated glomerular filtration rate, and severe clinical events.
Results: For 169 patients with available data, median age of first Fabry symptom manifestation was 12.7 years with peripheral pain as predominant first symptom, and diagnostic delay of 10.3 years from the first reported symptom. Female patients had high symptomatic burden during natural history follow-up, with 83% reporting peripheral pain, 69%-79% cold/heat intolerance or abnormal sweating, and 32% gastrointestinal symptoms. ERT-recipients reported similar age at first symptom as ERT-naïve patients but they were older at diagnosis (median 39.2 vs 24.4 years, P  < .01) and last follow-up (median 43.4 vs 28.2 years, P  < .01). Reported Fabry symptom frequencies and abnormal echocardiography findings were higher in ERT-recipients. Functional renal assessments were normal and similar.
Conclusions: Female patients from Latin America have notable diagnostic delays and high symptomatic burden. ERT was prescribed late in females with advanced age at diagnosis and advanced disease. There remained many female patients who had been diagnosed at younger age, had substantial Fabry manifestations, but did not receive disease-specific treatment.
Competing Interests: A.M.M. is a Fabry Registry Board member and received research funds, travel support, and speaking fees from Sanofi Genzyme, Alexion, and Biomarin. G.C. has consulting arrangements with and received speaking fees from Sanofi Genzyme. He received travel support from Sanofi Genzyme and Takeda. F.M. is a Fabry Registry Board member and received honoraria for lectures and board meetings from Sanofi Genzyme and speaking fees from Takeda and Merck Serono. F.S‐O. is a Fabry Registry Board member and received research funds, travel support, and speaking fees from Sanofi Genzyme. R.A.V. is a Fabry Registry Board member and received travel support and speaking fees from Sanofi Genzyme. C.V. is a Fabry Registry Board member and received honoraria for lectures and board meetings from Sanofi Genzyme and speaking fees from Takeda. M.Y. is an employee of Sanofi Genzyme. J.M.P. received honoraria for presentations and board meetings from Sanofi Genzyme, Takeda, and Amicus Therapeutics.
Databáze: MEDLINE
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