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

## TL;DR

A young woman with both Alport Syndrome and Fabry Disease showed unusually rapid kidney disease progression due to a rare genetic combination.

## Contribution

This is the first confirmed case of coexisting Fabry disease and Alport syndrome, explaining accelerated kidney failure in a patient with the R112H variant.

## Key findings

- A patient with the R112H GLA variant showed rapid progression to end-stage renal disease.
- Native kidney biopsy revealed Alport-like lesions, confirmed by a COL4A4 pathogenic variant.
- The combination of FD and Alport syndrome likely caused the accelerated kidney decline.

## Abstract

Fabry disease (FD) is an X-linked lysosomal disorder caused by GLA mutations, typically associated with glycosphingolipid accumulation and a wide phenotypic spectrum. The p.R112H 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 R112H 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 COL4A4 variant (G912R), 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 R112H. 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