The Fabry Nephropathy in Patients with N215S Variant

Nephron. 2025;149(10):604-608. doi: 10.1159/000545611. Epub 2025 Apr 4.

Abstract

Background: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that affects both males and females. It is caused by pathogenic variants in the gene that encodes the enzyme α-galactosidase A, GLA. The classic form of the disease begins in childhood, presenting with a range of signs and symptoms that can lead to severe complications such as stroke, as well as cardiac and renal failure. In the late-onset form, the disease appears in adulthood, often with signs of cardiac involvement.

Summary: The N215S (p.Asn215Ser) missense mutation represents the most common late-onset variant in European countries. In these patients, cardiac involvement is usually more prominent than extracardiac signs and symptoms, which is why this form is often referred to as a cardiac variant. Renal involvement in the N215S variant has historically been considered infrequent and relatively mild, contributing little to the overall disease burden of late-onset FD, as it has not been thoroughly investigated.

Key messages: In this review, we examine Fabry nephropathy in patients with the late-onset N215S variant, providing an insight into the clinical and histopathologic aspects of renal involvement in these individuals.

Keywords: Cardiopathy; Cardiovascular outcomes; Fabry disease; Late onset; N215S; Renal outcome.

Publication types

  • Review

MeSH terms

  • Fabry Disease* / complications
  • Fabry Disease* / genetics
  • Fabry Disease* / pathology
  • Female
  • Humans
  • Kidney Diseases* / etiology
  • Kidney Diseases* / genetics
  • Kidney Diseases* / pathology
  • Male
  • Mutation, Missense
  • alpha-Galactosidase* / genetics

Substances

  • alpha-Galactosidase