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| DiseaseID |
HGD27 |
| Genetic
Disorder |
Familial Mediterranean Fever
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| Gene
Name |
MEFV (Mediterranean Fever) gene |
| Description |
Familial Mediterranean Fever (FMF) is an inherited disease, characterized by recurrent attacks of fever, inflammation of the abdominal lining (peritonitis), inflammation of the lining surrounding the lungs (pleurisy), painful, swollen joints (arthralgia and occasionally arthritis), and a characteristic ankle rash. This condition is also sometimes referred to as recurrent polyserositis or familial paroxysmal polyserositis.
FMF is considered a rare disease worldwide. However, it is very common in people of Sephardic (non-Ashkenazi) Jewish, Armenian, Arab and Turkish heritage. Among people with these backgrounds, about 1 in 200 has FMF. The availability of genetic testing has helped identify numerous cases among several additional populations with Mediterranean roots, including: Ashkenazi Jews, Italians, Greeks, Spaniards, and Cypriots, and occasional cases in a broad range of other ethnicities (Northern Europeans and Japanese).
FMF is characterized by relatively short, usually 1- to 3-day, episodes of fever accompanied with serositis, synovitis or skin rash. In some patients, attacks begin in infancy or very early childhood, but 80 to 90 percent of patients experience their first episode by age 20. Young children sometimes present with recurrent fevers alone. The frequency of FMF attacks is highly variable, both among groups of patients or for any individual patient, with the interval between attacks ranging from days to years. Moreover, the type of attack - whether abdominal, pleural or arthritic - may also vary over time. Between attacks, people commonly are symptom-free.
Other symptoms that may occur include inflammation of the lining surrounding the heart (pericarditis), inflammation of the testis (orchitis), benign, recurrent inflammation of the membrane that surrounds the brain and spinal chord (meningitis), headaches and amyloidosis. Amyloidosis occurs when a particular protein, called amyloid, builds up in various tissues of the body, primarily the kidney. Potentially, it is the most serious complication of FMF, causing kidney failure. In some cases the amyloidosis can develop even without overt attacks of FMF.
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| Symptoms |
Signs and symptoms of familial Mediterranean fever usually begin during childhood. In fact, 80 percent to 95 percent of all people diagnosed with FMF are younger than 20 years old. The signs and symptoms, collectively referred to as "attacks," often occur with little warning. Generally, the attacks last two to three days, reaching peak intensity within the first 12 hours. Typical signs and symptoms may include:
A sudden fever, ranging from about 100 to 104 F
Abdominal pain
Chest pain
Achy, swollen joints
Constipation followed by diarrhea
A rash on your legs, especially below your knees
Less common signs and symptoms may include:
Muscle aches
Inflammation of the female reproductive organs (pelvic inflammatory disease)
A swollen, tender scrotum
Inflammation of your blood vessels (vasculitis)
Attacks usually occur sporadically, although some people report that vigorous exercise or stress provokes their attacks. Symptom-free periods may be as short as a week or as long as months. Between attacks, you'll likely feel normal.
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| Causes |
The cause of familial Mediterranean fever is a gene defect on chromosome 16 (each person normally has 46 chromosomes, in 23 pairs). Although it's not certain exactly how this defect causes familial Mediterranean fever, it may be that people with a mutation in this gene don't make a protein that inhibits the inflammatory response in certain parts of the body.
Familial Mediterranean fever is inherited as an autosomal recessive trait, meaning that you must inherit the mutated gene from each parent in order to develop the condition. |
| Diagnosis |
In making a diagnosis of Familial Mediterranean Fever (FMF), doctors take all of these factors into account:
• Whether or not the patient has the clinical symptoms common for the disease and whether the symptoms are recurrent.
• How he or she responds to colchicine treatment (see "How is Familial Mediterranean Fever treated?" below).
• Usually a positive family history in people of Middle Eastern ancestry.
• The results of genetic testing.
Also helpful in establishing a correct diagnosis of FMF is the patient's ancestry. Testing for the following can also be helpful:
• Elevated white blood cell count, which is an indication of an immune response.
• Elevated erythrocyte sedimentation rate (ESR), which is an indication of an inflammatory response.
• Elevated plasma fibrinogen, which helps stop bleeding. An elevated amount would indicate that something might be wrong with this mechanism.
• Elevated serum haptoglobin, which would indicate that red blood cells are being destroyed, a common occurrence in rheumatic diseases, such as FMF.
• Elevated C-reactive protein, which is a special type of protein, produced by the liver, that is only present during episodes of acute inflammation.
• Elevated albumin in the urine, which is demonstrated by urinalysis. The presence of the protein albumin in the urine can be a symptom of kidney disease, along with microscopic hematuria (very small - microscopic - amounts of blood or blood cells in the urine), during attacks.
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| Treatment |
At present, there is no known cure for Familial Mediterranean Fever (FMF). Physicians can only treat the symptoms of the disease.
A common therapy for FMF is daily use of the drug colchicine, a medicine that reduces inflammation. This therapy has been successful in preventing attacks of fever in 75 percent of patients who take the drug regularly, and over 90 percent of patients demonstrate a marked improvement. Even if colchicine does not prevent the fever attacks, it does prevent the amyloidosis. However, compliance in taking colchicine every day is very important. If a patient stops taking the drug, an attack can occur within a couple of days.
Since the gene that causes FMF codes for the protein pyrin, researchers hope that by studying how this protein works they will ultimately develop improved treatments for FMF, and possibly for other conditions involving excess inflammation. |
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