Front Genet. 2026 Aug 4;17:1905397. doi: 10.3389/fgene.2026.1905397. eCollection 2026.
ABSTRACT
Fabry disease is an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, in which the kidney is a principal target organ and Fabry nephropathy is a major determinant of long-term outcome. Its genetic architecture is heterogeneous: GLA variant class, residual α-galactosidase A (α-Gal A) activity, lyso-Gb3 level (globotriaosylsphingosine, the deacylated metabolite of globotriaosylceramide [Gb3]), sex, age, X-linked mosaicism, renal vulnerability, and tissue susceptibility together shape renal and systemic phenotype and define the framework for precision surveillance. Fabry nephropathy serves as the clinical anchor for integrating endocrine and metabolic findings into precision surveillance. Rather than providing a broad Fabry disease review, we evaluate endocrine domains according to evidence strength and renal relevance. Thyroid dysfunction, reproductive health, and bone/vitamin D abnormalities currently have moderate support; pituitary findings, growth and puberty, and body composition remain limited; and glucose/lipid metabolism and inflammatory-metabolic profiling are exploratory. Endocrine and metabolic assessment should therefore be integrated into risk-adapted surveillance strategies alongside renal monitoring, particularly in genotype-positive children and females, in whom early disease trajectories and long-term organ involvement remain difficult to predict.
PMID:42609911 | PMC:PMC13480968 | DOI:10.3389/fgene.2026.1905397