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Background <p>Fabry disease (FD) is an X-linked sphingolipidosis caused by enzyme α-Galactosidase A (α-Gal A) deficiency due to pathogenic variants in <i>GLA</i> 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.</p> Methods <p>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.</p> Results <p>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%). <i>GLA</i> gene sequencing revealed two pathogenic variants, NM_000169.3(<i>GLA</i>):c.559&#xa0;A &gt; G (p.Met187Val) and NM_000169.3(<i>GLA</i>):c.679&#xa0;C &gt; T (p.Arg227Ter), and a variant of unknown significance (VUS) reclassificated to a likely pathogenic variant NM_000169.3(<i>GLA</i>):c.122&#xa0;C &gt; G (p.Thr41Ser). Cascade screening identified three additional women with FD.</p> Conclusion <p>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 <i>GLA</i> gene, particularly those with VUS and novel variants, as they pose challenges for diagnosis and treatment.</p>

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Screening of fabry disease in patients with left ventricular hypertrophy: a single-center study in Mexico

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月25日

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  • Dante Palacios Gutierrez,
  • Gabriela Meléndez-Ramirez,
  • Edith Liliana Posada Martínez,
  • Blanca Rebeca Ibarra-Ibarra,
  • Solange Gabriela Koretzky,
  • Maria Cecilia Escalante Seyffert,
  • Francisco Javier Roldán Gómez,
  • Aloha Meave Gonzalez Ramirez,
  • Lucía de Montserrat Sabido González,
  • Daniel Vera Ibarra,
  • Juan Luis Ortiz Herrera,
  • Karla Vázquez Fernández,
  • Daniela Ramirez de Jesús,
  • Enrique Alexander Berrios Barcenas

摘要

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.