From renal amyloid deposits to the identification of the culprit genes

Hereditary amyloidoses with renal involvement are classified in two groups. The first group is a growing family of autoinflammatory disorders characterized by recurrent fever attacks. Amyloidosis is caused by the deposition of amyloid A (AA) protein, which is a degradation product of a normal serum acute-phase protein: serum amyloid A (SAA). The prototype is familial Mediterranean fever (FMF). TNF Receptor Associated Periodic Syndrome (TRAPS) is a recently recognized periodic fever syndrome, differing from FMF in several characteristics: autosomal-dominant transmission, longer duration of attacks, and lack of response to colchicine prophylaxis. The second group comprises a variety of disorders, each characterized by the deposition of a specific mutant protein. The prototype is transthyretin amyloidosis (TTR). Identification of the form of amyloidosis has clinical implications. Therefore, in a patient with a history of recurrent fever attacks and AA amyloidosis, a diagnosis of FMF or TRAPS dictates appropriate genetic counseling and management. In patients with renal amyloidosis without a history of fever, identification of the mutant protein is therapeutically crucial; therefore, when the cell type that produces the precursor is (exclusively or mainly) the hepatocyte, a liver transplantation is to be considered.