The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants
Por:
Sánchez R., Ripoll-Vera T., López-Mendoza M., de Juan-Ribera J., Gimeno J.R., Hermida Á., Ruz-Zafra M.A., Torregrosa J.V., Mora A., García-Pinilla J.M., Fortuny E., Aguinaga-Barrilero A., Torra R.
Publicada:
9 ene 2023
Ahead of Print:
9 ene 2023
Resumen:
Background: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation. © 2023, The Author(s).
Filiaciones:
Sánchez R.:
Multidisciplinary Unit for Low Prevalence Diseases, Hospital General Universitario de Alicante, Alicante, Spain
Ripoll-Vera T.:
Hospital Universitario Son Llàtzer & IdISBa, Palma de Mallorca, Spain
López-Mendoza M.:
Hospital Universitario Virgen Del Rocio, Seville, Spain
de Juan-Ribera J.:
Hospital General Universitario de Elda, Elda, Spain
Gimeno J.R.:
Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
Hermida Á.:
Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Ruz-Zafra M.A.:
Hospital Serranía de Ronda, Ronda, Spain
Torregrosa J.V.:
Hospital Clínic, Barcelona, Spain
Mora A.:
Hospital General Universitario de Elche, Elche, Spain
García-Pinilla J.M.:
Hospital Universitario Virgen de La Victoria, IBIMA, Málaga, Ciber-Cardiovascular, Instituto de Salud Carlos III, Departamento de Medicina y Dermatología, Universidad de Málaga, Málaga, Spain
Fortuny E.:
Hospital Universitario Son Espases & IdISBa, Palma, Spain
Aguinaga-Barrilero A.:
Amicus Therapeutics, SLU, Madrid, Spain
Torra R.:
Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, Institut d’Investigació Biomèdica Sant Pau (IIB-SANT PAU), Barcelona, Spain
gold, Green Published, All Open Access, Gold, Green
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