Refractory focal segmental glomerulosclerosis caused by Alport syndrome detected by genetic testing after three...

A woman in her 50s with a three-decade history of biopsy-proven focal segmental glomerulosclerosis and a family history of end-stage kidney disease presented with worsening proteinuria and declining kidney function after three decades of immunosuppressive therapy. While a repeat kidney biopsy did not reveal findings diagnostic of Alport syndrome, genetic testing demonstrated a heterozygous mutation in COL4A5, which confirmed the diagnosis of X-linked Alport syndrome. The heterozygous in-frame deletion mutation may explain her intact hearing and relatively mild symptoms. Genetic testing enables diagnosis of Alport syndrome of various phenotypes, some of which cannot be diagnosed conventionally with clinical course and kidney biopsy. Genetic disorders including collagen IV nephropathy should be considered as a differential diagnosis in patients with focal segmental glomerulosclerosis, especially when a patient has early-onset proteinuria, a family history of kidney disease, syndromic features or proteinuria refractory to glucocorticoid treatment.