Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent, irregular, and self-limited attacks of chest and abdominal pain associated with fever The gene responsible for FMF is mapped on the short arm of 16p 13.3. It is also designated MEFV (ME for Mediterranean and FV for fever). Approximately 70% of patients with clinical manifestations of FMF are heterozygous and the most common missense mutation is M694V. Genetic testing for the FMF gene confirms the diagnosis of FMF
The pathogenesis of the disease is not completely understood, even though the FMF gene has been identified. The increased inflammation, cytokines and generated reactive oxygen species at FMF causes oxidant burden at the body. The oxidative stress generated is balanced by the anti-oxidants at the body
Definition
Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent, irregular, and self-limited attacks of chest and abdominal pain associated with fever It is the most common autoinflammatory disorder. It is an autosomal recessive disease. FMF predominantly affects the populations arising from the Mediterranean basin. Its phenotype includes recurrent attacks of fever and serositis. The Mediterranean fever gene (MEFV) mutations are responsible for the disease. Its protein product, pyrin, plays an essential role in the regulation of the inflammatory reactions
The term auto-inflammatory disease or periodic fever syndrome has been proposed to describe a group of disorders characterized by attacks of unprovoked inflammation without significant levels of either autoantibodies or autoreactive T-cells. The study of autoinflammatory disease has progressed from clinical characterization to genetic analysis and to definition of the functional defects FMF is the most frequent periodic fever syndrome and autosomal recessive disease not only affecting ethnic groups living around the Mediterranean basin, but also reported throughout the world’s populations. It is characterized by recurrent inflammatory febrile attacks, abdominal, chest or joint pain, myalgia and erysipelas-like skin lesions
History
FMF was first described in 1908 by Janeway and Mosenthal in a 6-year-old Jewish girl presenting withabdominal pain and recurrent fever In 1945 Siegal, a Jewish allergologist, described it as “benign paroxystic peritonitis”, his own clinical picture was similar to features presented by other five Jewish patients: they all had cutaneous signs, recurrent peritonitis and periodic fever attacks (
In 1950, two French researchers, Mamou and Cattan, studied the familiar pattern of this disease in Sephardic Jews, In the same period, reports this disease has been described as benign paroxystic polyserositis, Armenian’s disease, Siegal-Cattan-Mamou’s syndrome and Reimann’s periodic disease. In 1958, Heller defined the overall FMF clinical picture and studied its autosomal recessive inheritance with the associated nephropathy deriving from amyloidosis: he also created the name “FMF” This is the most common auto-inflammatory disease and the first one with the causing gene identified in 1997
3-Racial distribution:
It has been estimated that about 170,000 people worldwide are affected with FMF, though a restricted ethnic distribution has been observed in people living around the Mediterranean basin and in the ancient Mesopotamia: groups living around the Mediterranean basin, but also reported throughout the world’s populations. It is characterized by recurrent inflammatory febrile attacks, abdominal, chest or joint pain, myalgia and erysipelas-like skin lesions Armenians, non-Ashkenazi Jews (above all Sephardic Jews), Turks and Arabs (mostly North-Africans such as Moroccans) However because of many migrations during the past centuries the gene causing FMF has also been spread in Western Europe and patients have been reported in Brazil, China Australia, New Zealand and Japan The clinical picture of FMF in Arabs appears to be distinct, and the range and distribution of MEFV mutations are different from those noted in other ethnic groups. In North African Arabs with FMF, p.Met694Val was common among Moroccans (49%) and Tunisians (50%), while p.Met694Ile accounted for 80% of mutations in Algerian Arabs with FMF. The estimated MEFV mutation carrier frequency in North African Arabs is 1:100, considerably lower than among North African Jews
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