Coexistence of Alport Syndrome and Fabry Disease in a Female with R112H Variant: Early Progression of Fabry Nephropathy

Fabry disease (FD) is an X-linked lysosomal disorder caused by <i>GLA</i> mutations, typically associated with glycosphingolipid accumulation and a wide phenotypic spectrum. The <i>p.R112H</i> variant is generally linked to a non-classic predominantly renal phenotype with mild biochemical abnormalities and slow progression. We report the case of a young woman carrying the <i>R112H</i> mutation who exhibited early-onset kidney involvement and unusually rapid progression to end-stage renal disease. Clinical history, serial evaluations, and kidney biopsy findings initially supported a diagnosis of Fabry nephropathy; however, re-evaluation of the native kidney biopsy revealed marked remodeling and multilamellation of the glomerular basement membrane, suggesting Alport-like lesions. Subsequent genetic testing confirmed a heterozygous pathogenic <i>COL4A4</i> variant (<i>G912R</i>), indicating coexistence of Fabry disease and autosomal dominant Alport syndrome. This dual genetic condition likely accounted for the accelerated decline in kidney function, in contrast with the typically mild phenotype associated with <i>R112H</i>. Our literature review indicates that coexistence of these two inherited nephropathies has not previously been confirmed either histologically or genetically. This case underscores the importance of integrating genetic and ultrastructural assessment in patients with atypical or rapidly progressive renal disease.