[1]: 149  FMF is an autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene, which encodes a 781–amino acid protein called pyrin.

[13] For the criteria, typical attacks consist of all the following: recurrent (three or more episodes), febrile (rectal temperature of at least 38 °C), painful inflammation, and a short duration of 12 to 72 hours.

AA amyloid protein is produced in very large quantities during attacks and at a low rate between them, accumulating mainly in the kidney, heart, spleen, gastrointestinal tract, and thyroid.

[4] Virtually all cases are due to a mutation in the Mediterranean Fever (MEFV) gene on the chromosome 16, which codes for a protein called pyrin or marenostrin.

[12] The function of pyrin is not fully known, but in short, it is a protein that binds to the adaptor ASC and the proform of the enzyme caspase-1 to generate multiprotein complexes called inflammasomes in response to certain infections.

In healthy individuals, pyrin-mediated inflammasome assembly (which leads to the caspase 1) dependent processing and secretion of the pro-inflammatory cytokines (such as interleukin-18 (IL-18) and IL-1β) is a response to enterotoxins from certain bacteria.

[15] The gain-of-function mutations in the MEFV gene cause pyrin more active in the body, which increases inflammasome formation.

[12] However, steroid hormone catabolites (pregnanolone and etiocholanolone) have been shown to activate the pyrin inflammasome in vitro by interacting with the B30.2 domain (coded by exon 10).

[22] The diagnosis is clinically made based on the history of typical attacks, especially in patients from the ethnic groups in which FMF is more highly prevalent.

An acute phase response is present during attacks, with high C-reactive protein levels, an elevated white blood cell count, and other markers of inflammation.

A positive diagnosis is made if the patient presents with a typical, albeit milder, FMF attack within 48 hours.

[30] Dr Hobart Reimann, working in the American University in Beirut, described a more complete picture which he termed "periodic disease".