[Familial Mediterranean fever as representative autoinflammatory disease].
Familial Mediterranean fever (FMF) is the most common of the hereditary periodic fevers. FMF is an autosomal recessive disease that affects populations among non-Ashkenazi Jews, Arabs, Turks, and Armenians. Yet, it is observed worldwide, and approximately 90 FMF patients have been reported in Japan. FMF is caused by mutations in the MEFV gene, which encodes the pyrin protein. Pyrin protein is associated with the interleukin (IL)-1-related inflammation cascade and involved in the regulation of apoptosis and inflammation. The clinical characteristics of FMF attacks are fever, abdominal pain, chest pain, and arthritis as symptoms of serositis. Reactive or secondary AA amyloidosis is the most devastating complication of FMF. As amyloid slowly accumulates in various organs and tissues, organ dysfunction ensues prominently in the kidneys. Colchicine has been used in the treatment of FMF, and has markedly changed the course of the disease. Although over 80 mutations in the MEFV gene have been reported, the majority of cases are caused by four mutations in exon 10: M694V, M694I, V726A, and M680I. The majority of Japanese FMF patients are compound heterozygous for M694I/E148Q. E148Q, which is found in populations of Japanese and Chinese, is considered to be a functional polymorphism. It is intriguing that about 10% of Japanese FMF patients have the L110P mutation in addition to E148Q in the same allele. Allelic frequencies of MEFV mutations and polymorphisms in 500 normal Japanese individuals were 0% for M694I and 23% for E148Q, respectively. In conclusion, FMF is not a rare disease in Japan, and it is necessary to consider FMF when a patient experiences recurrent attacks of fever and serositis.
Yamazaki
Kazuko
K
Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University, Matusmoto 390-8621, Japan.
Yamazaki
Takashi
T
Masumoto
Junya
J
Suzuki
Ayako
A
Yazaki
Masahide
M
Agematsu
Kazunaga
K
D000686:Amyloidosis / Q000209:etiology; D003078:Colchicine / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1; D009154:Mutation; D011110:Polymorphism, Genetic; D000071198:Pyrin
D003598:Cytoskeletal Proteins; D007375:Interleukin-1; C000604192:MEFV protein, human; D000071198:Pyrin; D003078:Colchicine