Phenotype-Genotype in Colombian women with Anderson-Fabry disease

Claudia Colmenares ² Claudia C Colmenares-Mejia ¹ Lina J. Moreno ³ Ana Lorenza Valencia ⁴

¹Fundación Cardiovascular De Colombia. Biomedical science PhD student. Universidad del Valle, Colombia
²Fundacion Cardiovascular De Colombia, Colombia
³Clínica Nueva de Cali, Medicarte SAS, Promovida IPS, Fundación Clínica Club Noel. Universidad Libre, Universidad Santiago de Cali, Universidad del Valle., Colombia
⁴E.S.E Hospital Departamental Universitario Santa Sofia de Caldas y Centro Visual Moderno., Colombia

Background: Fabry disease (FD) is an X-linked inherited lysosomal disease associated with pathogenic variants in the gene GLA encoding for the enzyme α-galactosidase A (α-Gal A). Clinical presentation in women is heterogeneous due to random X-chromosome inactivation and possibly epigenetic events. The aim of this study is to describe disease characteristics and associated management in women with pathogenic variants in the GLA gene in a Colombian cohort.

Methodology: Retrospective cross-sectional study in Colombian women with FD confirmed by molecular study. Demographic data, age of onset of symptoms-signs, organ involvement, diagnostic information and treatment were collected.

Results: 37 women were included. The median age was 33 years (IQR 23 - 56); 78.4% (n=29) were identified by family tree screening presenting classic phenotype (75.7%, n=28). Most frequent genetic variant was c.239G>A p. Gly80Asp (37.8%, n=14) with similar distribution between classic/non-classic phenotype (39.3%, n=11 vs 33.3%, n=3). In all cases variants were missense. 94.6% (n=35) had major organ involvement and 67.6% (n=25) had typical Fabry signs (angiokeratoma, cornea verticillate or increased lyso-Gb3). CNS (depression: 48.6%, n=18) and renal (albuminuria: 48.6%, n=18) were mainly affected. 30 (81.1%) patients received specific therapy [ERT alpha: n=12 (32.4%); ERT beta: n=3 (8.1%); Chaperone first line: n=12 (32.4%)]. Women with non-classical phenotype presented higher frequency of cold/heat intolerance (n=4, 44.4%). In untreated group (n=7, 18.9%) there was a greater reduction in exercise tolerance (n=3, 42.9%) and albuminuria (n=4, 57.1%).

Discussion: In this study a high percentage of women with pathogenic variants have severe signs and symptoms of FD and receive specific, but late-onset treatment. Still a significant number of women, even with the same profile as those treated, who may be eligible for treatment, remain untreated. The reasons for this need further research.