Meta-Analysis On The Role Of Migalastat In Fabry’s Disease: A Rare Cardiovascular Disorder

Abstract

Background: Fabry disease is an X-linked lysosomal storage disorder caused by GLA gene mutations causing α-galactosidase(GAL) A deficiency and accumulation of glycosphingolipids. Cardiac involvement, like concentric left-ventricular hypertrophy (LVH) and arrhythmia, is a major cause of morbidity. Migalastat is an oral pharmacologic chaperone that stabilizes amenable α-Gal A variants and restores enzyme function. This meta-analysis evaluated the efficacy and safety of migalastat across clinical studies.

Methods: The meta-analysis was done in accordance with PRISMA 2020 guidelines. PubMed Central and ClinicalTrials.gov were searched (2006–2025) for full length randomized, observational, and registry studies and clinical trials on migalastat in Fabry disease. Random-effects model (DerSimonian–Laird) was used for analysis. Outcomes assessed are: Left ventricular mass index(LVMI), change in plasma lyso-Globotriaosylsphingosine (Gb3), enzyme activity and adverse events.

Results: Fourteen independent studies on 382 Fabry patients treated with migalastat were analyzed. The pooled mean change in LVMI was +1.68 g/m² (95% CI −1.88 to +5.25), plasma lyso-Gb3 decreased by 0.16 ng/mL (95% CI −2.30 to +1.98), and mean eGFR decreased by 4.49 mL/min/1.73 m² (95% CI −7.31 to −1.68). α-Gal A activity showed a small nonsignificant rise. The pooled adverse-event rate was 76.9%,  serious adverse events occurred in 18.5% of patients.

Conclusion: Migalastat showed sustained biochemical stability, cardiac and renal preservation, and a favorable safety profile. This supports its role as an effective genotype-specific oral therapy for Fabry disease.