Screening of fabry disease in patients with left ventricular hypertrophy: a single-center study in Mexico
In brief
Fabry screening found three affected women among 205 patients with LVH
In this single-center Mexican study, genetic testing identified Fabry disease in three of 205 patients with unexplained left ventricular hypertrophy (1.5%); cascade screening then found three more affected women. The findings support considering genetic testing in women with this heart finding, but the small referral-center sample and uncertain genotype-phenotype links limit what can be concluded about prevalence and treatment.
- Journal
- Orphanet journal of rare diseases (Q1)
- Published
- 25 July 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Dante Palacios Gutierrez, Gabriela Meléndez-Ramirez, Edith Liliana Posada Martínez, Blanca Rebeca Ibarra-Ibarra, Solange Gabriela Koretzky, Maria Cecilia Escalante Seyffert, et al.
- PMID
- 42919303
- DOI
- 10.1186/s13023-026-04506-z
Why clinicians should know about it
- Picked for Genetics (clinical) (paper of the day, 26 October 2026): Fabry case-finding, variant reclassification, and cascade screening
Abstract
BACKGROUND: Fabry disease (FD) is an X-linked sphingolipidosis caused by enzyme α-Galactosidase A (α-Gal A) deficiency due to pathogenic variants in GLA gene. Progressive glycosphingolipid accumulation leads to subsequent myocyte injury, which frequently induces concentric remodeling and manifests as left ventricular hypertrophy (LVH). This study aims to describe the prevalence of FD in patients with LVH diagnosis in a Mexican population. METHODS: Consecutive and unrelated patients with echocardiographic evidence of left ventricular hypertrophy (LVH) without known cause were screened for FD in a Mexican cardiology referral center. Globotriaosylsphingosine (lyso-Gb3) levels and α-Gal A activity were measured using the dry blood spot method in all male individuals. Patients with positive dried blood spot testing and female patients were confirmed by single-gene sequencing. RESULTS: 205 patients with LVH (48.5 ± 18.7 years) were included. Of these, 53% were male, 60% were in NYHA functional class I, and 43% were asymptomatic. Dyspnea was the most frequently reported symptom, occurring in 26% of cases. Among study participants, three women were diagnosed with FD (1.5%). GLA gene sequencing revealed two pathogenic variants, NM_000169.3(GLA):c.559 A > G (p.Met187Val) and NM_000169.3(GLA):c.679 C > T (p.Arg227Ter), and a variant of unknown significance (VUS) reclassificated to a likely pathogenic variant NM_000169.3(GLA):c.122 C > G (p.Thr41Ser). Cascade screening identified three additional women with FD. CONCLUSION: These results emphasize the need for genetic screening for FD in female individuals with LVH. Further studies are needed to understand genotype-phenotype correlations in females with genetic variants in the GLA gene, particularly those with VUS and novel variants, as they pose challenges for diagnosis and treatment.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.