Gelsolin amyloidosis presenting with nephrotic syndrome: a case report and molecular insights

Familial Amyloidosis of Finnish type (FAF) is a rare autosomal dominant hereditary amyloidosis associated with genetic variants of gelsolin. This condition is characterized by ophthalmologic abnormalities, progressive cranial neuropathy, and cutis laxa, while renal impairment is rare. We report a gelsolin amyloidosis in a 58-year-old man with nephrotic syndrome and slowly progressive kidney dysfunction, associated with a gelsolin gene mutation (c.480C > A, p.Asn160Lys). Initial renal biopsy showed segmental IgA deposition, moderate mesangial expansion with weak PAS positivity, and parallel bundles of 10 nm fibrils, but only trace Congo red staining. A second biopsy 2 years later revealed IgA-dominant deposition, nodular sclerosis, similar fibrils, glomerular basement membrane lamination, and weakly positive Congo red. The diagnosis of gelsolin amyloidosis was confirmed by mass spectrometry and immunohistochemistry. Clinically, the patient had no neuropathy or family renal disease but presented with gastrointestinal symptoms, and endoscopy confirmed vascular amyloid deposition. Molecular structure analysis suggested that the mutation may loosen the protein structure while preserving its calcium-binding ability. Combining with the literature, we discuss the clinicopathological features and predicted protein functions of mutated gelsolin, aiming to elucidate its pathogenic mechanisms and deepen the understanding of hereditary amyloidosis.