Ref Robbins 9/e p259 Familial (Hereditary) Amyloidosis A variety of familial forms of amyloidosis have been described; most are rare and occur in limited geographic areas. The best-characterized is an autosomal recessive condition called familial Mediterranean fever. This is a febrile disorder characterized by attacks of fever ccompanied by inflammation of serosal surfaces, includ- ing peritoneum, pleura, and synol membrane. This dis- order is encountered largely in persons of Armenian, Sephardic Jewish, and Arabic origins. It is associated with widespread tissue involvement indistinguishable from reactive systemic amyloidosis. The amyloid fibril proteins are made up of AA proteins, suggesting that this form of amyloidosis is related to the recurrent bouts of inflamma- tion that characterize this disease. The gene for familial Mediterranean fever is called pyrin and encodes a protein that is a component of the inflammasome (Chapter 2). Patients have gain-of-function mutations in pyrin that result in constitutive overproduction of the pro- inflammatory cytokine IL-1 and persistent inflammation. In contrast with familial Mediterranean fever, a group of autosomal dominant familial disorders is characterized by deposition of amyloid predominantly in the peripheral and autonomic nerves. These familial amyloidotic poly- neuropathies have been described in kindreds in different pas of the world--for example, in Pougal, Japan, Sweden, and the United States. As mentioned previously, the fibrils in these familial polyneuropathies are made up of mutant forms of transthyretin (ATTRs).