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 in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. The length of time between attacks is also variable. Without treatment to help prevent attacks and complications, a buildup of certain protein deposits (amyloidosis) in the body's organs and tissues may occur, which can lead to kidney failure.

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

Mutations in the MEFV gene cause 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 is involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops the inflammatory response to prevent damage to its own cells and tissues.

Mutations in the MEFV gene reduce the activity of the pyrin protein, which disrupts control of the inflammation process. An inappropriate or prolonged inflammatory response can result, usually accompanied by fever and pain in the abdomen, chest, or joints.

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

Familial Mediterranean fever is almost always inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

In rare cases, this condition appears to be inherited in an autosomal dominant pattern, in which one copy of the altered gene in each cell is sufficient to cause the disorder and affected individuals often inherit the mutation from one affected parent. However, there are other possible explanations of this apparent pattern. A gene mutation that occurs frequently in a population may result in a disorder with autosomal recessive inheritance appearing in multiple generations in a family, a pattern that mimics autosomal dominant inheritance. If one parent has familial Mediterranean fever (with two mutations in the MEFV gene) and the other parent is an unaffected carrier (with one mutation in the MEFV gene), it may appear as if the affected child inherited the disorder only from the affected parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance.