RT Journal Article
T1 Fabry disease in the Spanish population: observational study with detection of 77 patients.
A1 Vieitez, Irene
A1 Souto-Rodriguez, Olga
A1 Fernandez-Mosquera, Lorena
A1 San Millan, Beatriz
A1 Teijeira, Susana
A1 Fernandez-Martin, Julian
A1 Martinez-Sanchez, Felisa
A1 Aldamiz-Echevarria, Luis Jose
A1 Lopez-Rodriguez, Monica
A1 Navarro, Carmen
A1 Ortolano, Saida
K1 Enzymatic screening
K1 Fabry disease
K1 GLA complex haplotype
K1 Intronic variants
K1 Lysosomal storage disorders
AB Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence of this rare disease is underestimated due to delayed diagnosis. Moreover, the management of the identified subjects is often complicated by the detection of variants of unclear diagnostic interpretation, usually identified in screening studies. We performed an observational study based on biochemical and genetic analysis of 805 dried blood spot samples from patients with clinical symptoms or family history of this pathology, which were collected from 109 Spanish hospitals, all over the country. We identified 77 new diagnosed patients with mutations related to classical Fabry disease, as well as 2 subjects with c.374A > T; p.His125Leu, a possible new mutation that need to be confirmed. Additionally, we detected 8 subjects carrying genetic variants possibly linked to late onset Fabry disease (p.Arg118Cys and p.Ala143Thr), 4 cases with polymorphism p.Asp313Tyr and 36 individuals with single nucleotide polymorphisms in intronic regions of GLA. Five of the identified mutations (c.431delG; c.1182delA; c.374A > T; c.932 T > C; c.125 T > A; c.778G > A), which were associated with a classical phenotype have not been previously described. Moreover 3 subjects presenting complex haplotypes made up by the association of intronic variants presented impaired levels of GLA transcripts and Gb3 deposits in skin biopsy. Enzymatic screening for Fabry Disease in risk population (2 or more clinical manifestations or family history of the disease) helped to identify undiagnosed patients and unravel the impairment of GLA expression in some subjects with complex haplotypes.
YR 2018
FD 2018-04-10
LK http://hdl.handle.net/10668/12324
UL http://hdl.handle.net/10668/12324
LA en
DS RISalud
RD Apr 15, 2025