A complex case of renal amyloidosis with a rare co-occurrence of 2 mutations in separate hereditary periodic fever syndrome-related genes

A 41 year-old male was admitted because of nephrotic syndrome associated with renal impairment and arterial hypertension. Renal biopsy showed a complete subverting of renal architecture with eosinophilic, amorphous deposits which stained positive for Congo red and were positive for antibodies against AA-amyloid. Abdominal fat pad aspirate confirmed the diagnosis of AA amyloidosis.

Despite high values of serum amyloid A (SAA), surprisingly medical history, physical examination and all tests failed to identify any underlying inflammatory disease, even asymptomatic, at presentation and during the whole follow-up period.

The patient carried a mutation (Glu148Gln) in theMEFV gene,and a mutation (Arg92Gln) in theTNFRSF1Agene, both in heterozygosity. The patient has never complained of the typical features of the Familial Mediterranean fever or of the TNF receptor-associated periodic syndrome. The patient's father carried the same mutations. His father's medical history was unremarkable; renal tests, acute-phase reactants and SAA were normal.

During a trial with colchicine (while the patient was also taking atorvastatin) SAA decreased, renal function continued to deteriorate and proteinuria remained high; no cardiac involvement was detected. Six months later our patient developed rhabdomyolysis, thus accelerating the decline of renal function and requiring the start of dialysis.