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.