Background: Genetic mutations in alpha-actinin 4 (ACTN4) are one cause of familial focal segmental glomerulosclerosis (FSGS) and steroid-resistant nephrotic syndrome (SRNS) in early adulthood, eventually progressing to end-stage kidney disease. Early initiation of renin-angiotensin-aldosterone system inhibitors (RAASis) is reported to delay progression of several forms of familial FSGS and SRNS; however, no cases involving ACTN4 mutations have been reported.
Case presentation: A 16-year-old boy was admitted to our hospital for a detailed evaluation of proteinuria that first appeared during treatment for Duchenne muscular dystrophy (DMD) and persisted for 1 year. He had been treated with prednisolone and an angiotensin-converting enzyme inhibitor (ACEi) for 2 years prior to the onset of persistent proteinuria. A renal biopsy revealed segmental sclerosis in 1 of 40 glomeruli, with effaced foot processes observed under electron microscopy. Genetic testing identified ACTN4 mutation (c·776C > T, p.T259I), leading to a diagnosis of autosomal dominant FSGS caused by ACTN4 mutation. After the first appearance of proteinuria, the patient's renal function and urinary protein levels remained stable for following 7 years.
Conclusions: We report a case of adolescent-onset FSGS with ACTN4 mutation diagnosed during ACEi therapy for the prevention of DMD-associated cardiomyopathy. The patient exhibited stable renal function and no disease progression compared with his father and previously reported cases with the same variant. This is the first reported case of early RAASi induction for treating ACTN4-associated FSGS with long-term stable renal function.
Keywords: Alpha-actinin-4; Angiotensin-converting enzyme inhibitor; Cyclin D1; Focal segmental glomerulosclerosis; Inherited kidney disease; Nephrotic syndrome; Steroid-resistant nephrotic syndrome.
© 2025. The Author(s).