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Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is characterized by recurring episodes of painful inflammation in the abdomen, chest, or joints. FMF occurs predominantly in Sephardic Jews, though people of Ashkenazi Jewish origin can also be affected – often with a milder form of the condition. The symptoms of FMF can be easily treated in the vast majority of patients.

If you have just received a diagnosis there is help and support available - please see ‘Further information and support’ below for links to valuable resources. It is also important to note that not every person with this condition experiences all the symptoms described and it is worth talking to your doctor or other relevant healthcare specialists to discuss you or your family member’s specific case.

Inheritance

Familial Mediterranean fever is an autosomal recessiveRecessive disorders require both parents to carry a specific disorder-related mutation and pass it on to their child for the disorder to be inherited condition.

Prevalence

Familial Mediterranean fever is most commonly found in Sephardi JewsDescendants of the Jews who lived in Spain or Portugal before 1492. The term is now often applied to refer to anyone Jewish of non-Ashkenazi ancestry (including the ancestrally distinct group of Middle Eastern Jews) where the disease frequency is approximately 1 in 200.

The carrier frequencyNumber that describes how many people in a population are carriers (have one altered copy of a gene and one normal copy of the same gene) for a genetic disorder. Carriers for recessive disorders are unaffected but are at risk of passing on the disorder to their children. among Jews from Libya, Algeria, Tunisia and Morocco is approximately 1 in 6, whilst in Jews from Iraq and Turkey the carrier frequency is approximately 1 in 13.

The carrier frequency among Ashkenazi Jews is generally thought to be much lower, although a carrier rate of up to 1 in 5 has been reported in some studies.

Although the carrier frequency in the general population is very low, other Mediterranean populations e.g. Armenians, Arabs and Turks have a similar disease frequency to that of Sephardic Jews. 

Symptoms

Familial Mediterranean fever is often diagnosed in childhood when an affected individual experiences short periodic pain episodes lasting between 12 and 72 hours. The frequency and type of these episodes varies greatly; some people have them every few days, whilst others only every few years. People with FMF usually have no other symptoms between the pain episodes.

Some common signs and symptoms of FMF are:

  • Abdominal pain (which can be severe but goes away after a few days)
  • Fever – present with other symptoms e.g. during pain episodes
  • Chest pain - symptoms of pleurisy that resolve within a few days
  • Joint pain (usually FMF affects only one joint like the knee, ankle or hip)
  • Arthritis (i.e. persistent joint symptoms associated with more severe joint inflammation)
  • Rashes and irritation of the skin
  • Amyloidosis, predominantly causing kidney failure, it occurs more frequently in Sephardic Jews. This can be prevented by long-term treatment with colchicine (see below).

Please click on the titles to open and close the following information sections.

Familial Mediterranean fever is caused by a mutationA mutation refers to a structural change in a gene. It can be an alteration to a gene’s size, arrangement, or molecular sequence in a gene which codes for a protein called pyrin. This protein is found in white blood cells and is thought to play a key role in regulating the body’s inflammatory response.  Damage to this protein disrupts control of the inflammatory process, causing episodes of painful inflammation and fever.

There are many different mutations possible in this gene, some of which cause a more serious form of FMF than others. The most severe mutations tend to be common amongst Sephardic Jews whist the milder mutations are more common in the Ashkenazi Jewish population.

The symptoms of FMF and the long-term risk of developing amyloidosis can be prevented very effectively by daily treatment with a drug called colchicine.  The effective dose varies between patients, and it is solely a preventative treatment that must be taken on a regular daily basis.

People with FMF should have an annual check-up to monitor their compliance to the treatment.

FMF is not known to affect a persons’ lifespan, especially when treated. The treatment is life-long, with the dual purpose of preventing the majority of attacks, and crucially the risk of amyloidosis.  Colchicine is remarkably safe, and women are nowadays advised to continue the treatment during pregnancy.

In very few people with FMF, colchicine drug is poorly tolerated or it is not very effective.  Poor compliance to the treatment is the most common cause of lack of effect.  Alternative drugs that require injection are in development.

Familial Mediterranean fever can be diagnosed by a doctor familiar with the symptoms. The diagnosis is confirmed by a positive response to colchicine treatment, and through genetic testing.

Carrier testing and prenatal diagnosis for FMF are also now possible, though since the disorder is easily treated, appropriate counselling is vital.  The test identifies the most common mutations among people of Sephardic and Ashkenazi Jewish origin. The detection rate for carriers of Sephardic Jewish ancestry is approximately 95%, whilst the detection rate for Ashkenazi Jews is 90%.

For more details about testing, please refer to the testing section.

FMF support group – Yahoo Group
An online support group for individuals and their families who are affected by Familial Mediterranean fever (FMF).

Stop CAID Now
(Stop childhood autoinflammatory diseases now)
This USA based charity aims to educate, raise awareness, and fund researchers who are committed to finding a cure for CAIDs.

Ariella’s Story 
Click on the link above to watch a short video of Ariella telling her personal story of her experiences living with FMF.

To find out more about general resources relevant to Jewish genetic disorders, please visit our resources and support section.

 

Written by Jnetics.
Approved by Professor Philip N Hawkins, Clinical Director of the National Amyloidosis Centre, Royal Free Hospital
Last review: 8.1.2015