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Familial Mediterranean fever

What is familial Mediterranean fever?

Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. These episodes are often accompanied by fever and sometimes a rash. The first episode usually occurs by the age of 20, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity and length of time between attacks. A buildup of protein deposits (amyloidosis) occurs in some cases of familial Mediterranean fever and can lead to kidney failure if left untreated.

How common is familial Mediterranean fever?

Familial Mediterranean fever primarily affects populations originating in the Mediterranean region, particularly people of Armenian, Arabic, Turkish, and Jewish ancestry. The frequency of affected individuals in these populations ranges from 1 in 250 people to 1 in 1,000 people. This disorder is less common in other populations.

What genes are related to familial Mediterranean fever?

Mutations in the MEFV gene cause familial Mediterranean fever.

Normal variations in the SAA1 gene modify the course of familial Mediterranean fever.

The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin), which is found in white blood cells. This protein probably helps to limit or stop the inflammation process. Mutations in the MEFV gene can lead to reduced activity of the pyrin protein, which disrupts control of the inflammation process. With impaired control, an inappropriate or prolonged inflammatory response can occur, usually accompanied by fever and pain in the abdomen, chest, or joints.

Some evidence suggests that a particular version of the SAA1 gene (called the alpha variant) may increase the risk of amyloidosis among people with familial Mediterranean fever.

How do people inherit familial Mediterranean fever?

This condition is inherited in an autosomal recessive pattern, which means both copies of the MEFV gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

In rare cases, familial Mediterranean fever appears to be inherited in an autosomal dominant pattern, which means one copy of an altered MEFV gene is sufficient to cause the disorder. In these cases, an affected person has one parent with the condition.

Familial Mediterranean Fever on Wikipedia

'''Familial Mediterranean fever''' (FMF) is a genetic disorder inflammation disorder that affects groups of patients originating from around the Mediterranean Sea (hence its name). It is prominently present in the Armenia people (up to 1 in 7 affected), Sephardi Judaism (and, to a much lesser extent, Ashkenazi Jews), people from Turkey, the Arab countries and Lebanon.

Clinical symptoms

Attacks

There are seven types of attacks. 90% of all patients have their first attack before they are 20 years old. All develop over 2-4 hours and last anytime between 6 hours and 4 days. Most attacks involve fever: # Abdominal attacks, featuring abdominal pain affecting the whole abdomen with all signs of acute abdomen (e.g. appendicitis). They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported. # Joint attacks, occurring in large joints, mainly of the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks. # Chest attacks with pleuritis (inflammation of the pleural lining) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40%, but pericarditis is rare. # Scrotum attacks due to inflammation of the tunica vaginalis. This occurs in up to 5% and may be mistaken for acute scrotum (i.e. testicular torsion) # Myalgia (rare in isolation) # Erysipelas (a skin reaction on the legs, rare in isolation) # Fever without any symptoms (25%)

Complications

amyloidosis with renal failure is a complication and may develop without overt crises. AA (amyloid protein) is produced in very large quantities during attacks and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract ...   [ Read More ]


External Resources

Scientists Identify Gene for Familial Mediterranean Fever - An article covering the discovery of the gene causing the disease.

Genes and Diseases (NCBI) - Gene involved and etiology of Familial Mediterranean Fever (FMF).

Jewish Genetic Disorders (MazorNet) - Overview of Familial Mediterranean Fever, screening and testing information. Support and resources.

Diagnosis of Familial Mediterranean Fever - Explains the Molecular Genetics Method used in the diagnosis.


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