MEFV

MEFV is a human gene that encodes the protein pyrin (also known as marenostrin), which plays a role in regulating the innate immune response and the inflammasome pathway that controls interleukin-1 beta (IL-1β) production. The gene is located on chromosome 16p13.3.

Mutations in MEFV are the primary cause of Familial Mediterranean Fever (FMF), an autoinflammatory disorder characterized by recurrent fevers and serosal inflammation, such as abdominal, chest, or joint pain. The inheritance pattern is usually autosomal recessive, but penetrance can vary and some individuals with a single mutated allele may exhibit symptoms.

Common disease-associated variants include M694V, M680I, V726A, M694I, and E148Q. M694V is frequently linked with more severe disease and a higher risk of complications like secondary amyloidosis, though genotype-phenotype correlations are not absolute.

Pathophysiology involves dysregulation of the pyrin inflammasome, leading to excessive activation of inflammatory pathways and IL-1β production during attacks. This results in the episodic inflammatory symptoms seen in FMF.

Diagnosis typically relies on clinical criteria supported by genetic testing for MEFV mutations, particularly in individuals from populations with higher carrier frequencies (such as Mediterranean, Arab, Jewish, and Turkish groups). During attacks, inflammatory markers (CRP, ESR) are elevated, and serum amyloid A can increase with prolonged disease.

Treatment centers on preventing attacks and complications. Colchicine is the first-line therapy and reduces attack frequency and the risk of amyloidosis in most patients. For those who are colchicine-resistant or intolerant, IL-1 inhibitors (such as canakinumab or anakinra) may be used. Ongoing management focuses on reducing inflammation and monitoring for long-term complications.