Renal gelsolin amyloidosis as a rare cause of proteinuria: a case report and literature review.

BACKGROUND: Hereditary gelsolin amyloidosis (AGel amyloidosis) is a rare autosomal dominant systemic amyloidosis caused by mutations in the Gelsolin (GSN) gene encoding gelsolin. The condition is characterized by a triad of cranial nerve involvement, corneal lattice amyloidosis, and skin laxity, with a small proportion of cases involving the kidneys and heart. We report the first case of renal AGel amyloidosis associated with a c.487G > A mutation in the GSN gene, presenting as isolated proteinuria.

CASE PRESENTATION: A 55-year-old woman presented with proteinuria. She had a history of hypertension and diabetes but no family history of kidney disease. Physical examination revealed no abnormalities in the heart, eyes, nerves, or skin. Urinalysis showed moderate proteinuria (1975.5 mg/24h), and serum creatinine was normal (0.71 mg/dL). Renal biopsy revealed Congo red-positive glomeruli on light microscopy, with apple-green birefringence under polarized light. Electron microscopy showed randomly arranged fibrillar deposits in the glomeruli. Mass spectrometry analysis confirmed that the deposits were consistent with gelsolin protein. Genetic testing revealed a heterozygous missense mutation in the GSN gene (NM_198252.3; c.487G > A; p.Asp163Asn). The patient was diagnosed with AGel amyloidosis. Additionally, we compiled the phenotypic and genotypic characteristics of previously reported AGel amyloidosis cases.

CONCLUSION: We report a novel mutation in AGel amyloidosis with renal involvement. This case highlights the importance of renal biopsy, mass spectrometry analysis, and genetic testing in establishing a definitive diagnosis. It expands the known spectrum of GSN gene mutations and further supports the heterogeneity of the AGel amyloidosis phenotype.