Familial Mediterranean fever (FMF) is an inherited disorder that is passed down from parents to their children. Individuals who have FMF inherited a defective gene from their parents.
Each person has 46 chromosomes in 23 pairs. Chromosomes contain all of the genes inherited from an offspring's parents. FMF patients have a genetic defect (abnormality) on chromosome 16. However, researchers have not discovered exactly how this genetic defect causes FMF. It also remains unknown why the severity and duration of FMF attacks vary among patients.
The abnormal gene for FMF is inherited as an autosomal recessive trait. This means the patient must inherit one mutated gene from each parent in order to develop the disease. Individuals who only inherit one mutated gene and do not experience symptoms are called carriers. Although they do not have the disease, they can pass the mutated gene to their children.
Carriers have a 50% chance of passing the abnormal gene to each of their children. If both parents are carriers of FMF, there is a 25% chance that each of their children will have the disease and a 50% chance that each of their children will be a carrier.
General: Symptoms of familial Mediterranean fever (FMF) generally do not appear until the patient between five and 15 years old. Symptoms are collectively called attacks because they develop suddenly and only last about two to three days. Symptoms are typically the most intense within the first 12 hours of an attack. The length of time between attacks varies among patients. Sometimes the attacks are only a few weeks apart, while other times they are several months apart. In between attacks, patients do not experience any symptoms.
Common symptoms: Common symptoms of an attack include sudden fever (ranging from about 100-104 degrees Fahrenheit), chills, abdominal pain, chest pain, achy and swollen joints, rash on the legs, and constipation followed by diarrhea.
Less common symptoms: Less common symptoms include muscle aches, inflammation of the blood vessels, pelvic inflammatory disease in females (swollen female reproductive organs), and swollen and tender scrotum in males.
General: An estimated 80-95% of patients with familial Mediterranean fever (FMF) are diagnosed before the age of 20. There is currently no specific lab test to diagnosis FMF. Instead, a diagnosis is made after a physical examination and medical history are conducted along with blood tests. Genetic tests may also be performed.
Blood tests: Blood tests can be performed during an attack to help diagnose the disorder. During an attack, patients typically have elevated levels of white blood cells. Healthy individuals typically have 4,500-10,000 white blood cells per microliter of blood.
An erythrocyte sedimentation rate (ESR) test, which measures the rate that red blood cells settle in unclotted blood, may also be performed. Normal values for men younger than 50 years old are 15 millimeters/hour and less than 20 millimeters/hour for men older than 50. The normal values for women who are less than 50 years old are less than 20 millimeters/hour and less than 30 millimeters/hour for women older than 50. Patients with FMF will have elevated rates.
A fibrinogen blood test may also be performed. During the procedure, a small sample of blood is taken from the patient in order to measure the amount of fibrinogen (a coagulation factor) in the blood. Healthy individuals typically have 200-400 milligrams of fibrinogen per deciliter of blood. Elevated levels indicate FMF.
A C-reactive protein (CRP) test can be performed. A high or increasing amount of CRP in the blood suggests that the patient has inflammation. In a healthy patient, CRP is usually less than 10 milligrams/liter. Most inflammations result in CRP levels above 100 milligrams/liter.
Genetic test: The DNA (genetic makeup) from a sample of the patient's blood can be analyzed for mutations associated with FMF. However, genetic tests are not commonly used as a diagnostic tool because they do not identify all of the different gene mutations associated with the disorder. This procedure may be performed to determine whether a patient carries the gene. Although carriers do not have the disorder, they can pass the mutated gene on to their children.
Medical history: During a careful medical history, a healthcare provider will ask the patient if FMF has been diagnosed in family members. The patient's ethnicity should also be considered because patients of Mediterranean ancestry, including Sephardic Jews, Armenians, Turks, North Africans, Arabs, and less frequently, Greeks and Italians, are most likely to develop this disorder. However, FMF has also been diagnosed in other ethnic groups, including Ashkenazi Jews in the United States. Therefore, ethnicity alone cannot be used to diagnose or rule out the disorder.
Physical examination: During the physical examination, a healthcare provider will determine whether the patient's symptoms are characteristic of FMF. Such symptoms include recurrent fever, joint paint, abdominal pain, chest pain, and achy or swollen joints that occur in isolated episodes, lasting about two to three days.
General: Complications of familial Mediterranean fever (FMF) usually only occur in patients who are not receiving treatment or not following their treatment regimens. Therefore, patients should take medications exactly as prescribed by their healthcare providers to help prevent complications.
Amyloidosis: Amyloidosis is considered the most common complication of untreated FMF. This condition occurs when an abnormal protein called amyloid builds up in the body's tissues and organs, especially the kidneys. Amyloidosis that affects the kidneys may lead to a kidney disorder called nephrotic syndrome. Once the FMF is treated, symptoms of amyloidosis will begin to resolve.
Chronic arthritis: An estimated five percent of FMF patients develop chronic arthritis, which causes pain and inflammation of the joints. Chronic arthritis is typically treated with non-steroidal anti-inflammatories like celecoxib (Celebrex®). In sever cases, patients may need surgical hip or knee joint replacements.
General discomfort: If FMF is not properly treated, it can be extremely painful and may interfere with a patient's quality of life. Patients may be unable to perform normal daily activities when attacks occur.
Infertility: If inflammation associated with FMF is not properly treated, it can potentially lead to infertility, especially in women. Researchers estimate that about 33% of females are infertile, and 20-30% of women who become pregnancy have miscarriages.
Nephrotic syndrome: Nephrotic syndrome, a disorder in which the kidneys become damaged and do not function normally, may also occur if FMF is not properly treated. This occurs when abnormal levels of a protein called amyloid build up in the kidneys. Patients typically experience swollen hands and feet. Nephrotic syndrome is potentially life threatening because it may lead to blood clots in the kidneys or kidney failure. Patients with nephrotic syndrome typically receive different types of medications, including immunosuppressants, corticosteroids, and diuretics. Once FMF is adequately treated, patients will no longer need to receive additional treatment for nephrotic syndrome.