Abstract: TH-PO618

Gelsolin Amyloidosis (Familial Amyloidosis of Finnish Type) in a North American Kindred

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Salameh, Hassan A., Mayo Clinic, Rochester, Minnesota, United States
  • Ashrani, Aneel A, Mayo Clinic , Rochester, Minnesota, United States
  • Howard, Matthew, Mayo Clinic, Rochester, Minnesota, United States
  • Cornell, Lynn D., Mayo Clinic, Rochester, Minnesota, United States
  • Hogan, Marie C., Mayo Clinic, Rochester, Minnesota, United States
Background

Gelsolin amyloidosis is a rare form of systemic amyloidosis characterized by lattice corneal dystrophy, cranial nerve neuropathies and elastolysis. Renal involvement with nephrotic syndrome is rare. Early onset severe kidney disease has been reported in homozygotes and late onset slowly progressive forms in heterozygotes. It is usually caused by a gelsolin gene defect, namely a G640A previously known as G654A or G654T mutation.

Methods

We report a 74-year-old man presenting with CKD3 and nephrotic syndrome (NS). Medical history was significant for hypertension and lattice corneal dystrophy type II (LCD II) and family history of LCD II (son, mother, two maternal uncles and maternal aunts, (all of Lithuanian-Finnish heritage) ) and no family history of kidney disease. Exam showed periorbital and ankle edema. Serum creatinine was 2.1 mg/dL with eGFR 33 mL/min/1.73 m2 and 5.6 g proteinuria/24h. SPEP and UPEP were negative. Free light chains were mildly elevated. Kidney biopsy (KB) showed minimal Congo red positivity along with immunofluorescence findings revealed amyloidosis of undetermined type. Electron microscopy showed 10.8 nm fibrils focally replacing the glomerular basement membrane. No additional KB material was available for laser microdissection (LMD) and mass spectroscopy (MS). MS proteomics of fat aspirate material (with equivocal Congo red stain) typed the most abundant peptides were from GELS_HUMAN with p.D214N AA change identified. A heterozygous pathogenic variant c.640G>A (g.124073097; p.D214N also known as p.D187N) in the GSN gene was confirmed by Sanger sequencing consistent with familial amyloidosis Finnish type.

Conclusion

Our patient had an unusual presentation with renal and ophthalmic involvement and no neurologic or dermatologic manifestations. This report highlights (1) importance of MS evaluation in atypical amyloidosis cases (2) implications for management (therapies are now in pre-clinical studies) (3) genetic counseling implications for families; heterozygous cases have late onset slowly progressive disease and (4) in cases where there is insufficient KB tissue for MS analysis, fat aspirate material (a relatively minimally invasive procedure) permitted confirmation.