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. 2019 Aug 5;49(1):107-117.
doi: 10.1002/jmd2.12071. eCollection 2019 Sep.

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

Ana M Martins  1 , Gustavo Cabrera  2 , Fernando Molt  3   4 , Fernando Suárez-Obando  5 , Régulo A Valdés  6 , Carmen Varas  4 , Meng Yang  7 , Juan M Politei  8
Affiliations

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

Ana M Martins et al. JIMD Rep. .

Abstract

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.

Keywords: Fabry disease; Latin America; diagnostic delay; enzyme replacement therapy; females; registry.

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Conflict of interest statement

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.

References

    1. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. - PMC - PubMed
    1. Schiffmann R, Warnock DG, Banikazemi M, et al. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant. 2009;24:2102‐2111. - PMC - PubMed
    1. Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007;9:34‐45. - PubMed
    1. Wilcox WR, Oliveira JP, Hopkin RJ, et al. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry registry. Mol Genet Metab. 2008;93:112‐128. - PubMed
    1. Echevarria L, Benistan K, Toussaint A, et al. X‐chromosome inactivation in female patients with Fabry disease. Clin Genet. 2016;89:44‐54. - PubMed

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