Am J Case Rep. 2026 Aug 18;27:e952758. doi: 10.12659/AJCR.952758.
ABSTRACT
BACKGROUND Fabry disease (FD) is a rare X‑linked lysosomal disorder in which long‑term cardiac outcomes, particularly in heterozygous females, remain incompletely defined. The N224S alpha-galactosidase A gene (GLA) variant is recognized as pathogenic, yet its cardiac phenotype and response to prolonged migalastat therapy are not well characterized. Although clinical trials and observational studies have reported variable cardiac responses to migalastat, real‑world longitudinal data beyond 5 years remain limited. Understanding long‑term structural and functional changes is especially important in patients with pre‑existing cardiac involvement, where distinguishing favorable remodeling from fibrosis‑related progression can be challenging. CASE REPORT We describe a 9‑year follow‑up of a 71‑year‑old heterozygous woman with FD due to the N224S mutation treated with migalastat. Serial transthoracic echocardiography demonstrated a sustained reduction in left ventricular mass index (LVMI) over long‑term therapy. Left ventricular systolic function remained preserved throughout follow‑up, and there was no evidence of progressive structural deterioration. Available Doppler‑derived diastolic indices, including a gradual decline in early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e'), suggested improving left ventricular filling pressures over time. Although LVMI showed minor year‑to‑year variability, these changes were consistent with expected technical or physiological variation and did not alter the clear long‑term downward trend. CONCLUSIONS This case provides real‑world evidence of favorable long‑term cardiac remodeling during migalastat therapy in a heterozygous woman with the N224S variant. The sustained reduction in LVMI, preserved systolic function, and improving diastolic indices together indicate a durable cardiac response and extend the limited longitudinal data available for variant‑specific outcomes in FD.
PMID:42608886 | PMC:PMC13499433 | DOI:10.12659/AJCR.952758