How is familial mediterranean fever inherited

Bybee, M. Akar, M. Pepys, M. Tunca, P. Familial Mediterranean fever FMF is classically an autosomal recessive periodic inflammatory disease occurring in Mediterranean and Middle Eastern populations. It is caused by mutations affecting both alleles of MEFV , a gene that encodes pyrin marenostrin , an uncharacterized neutrophil protein. Familial Mediterranean fever FMF is an inherited inflammatory disease that is principally recognized in Jewish, Armenian, Turkish and Arab populations.

The characteristic intermittent clinical episodes of fever, peritonitis, pleurisy, rashes and arthritis are variable in their pattern, frequency, intensity and age of onset, as is the proportion of FMF patients in different ethnic groups who develop AA amyloidosis.

However, few family studies incorporating MEFV genotyping have been performed. We report here comprehensive analysis of MEFV in five families from different ethnic backgrounds. We studied five families who had been previously evaluated in our clinics. Eight were tested for amyloidosis using radiolabelled serum amyloid P component scintigraphy. Open boxes are asymptomatic FMF gene carriers. Shaded boxes are asymptomatic carriers of compound dual allele MEFV mutations. Shaded boxes are asymptomatic carriers of compound single allele MEFV mutations.

Open boxes are clinically healthy individuals. Shaded boxes are deceased relatives with clinical histories consistent with FMF.

Exon 10 was sequenced in all cases, and additional regions of MEFV were characterized as necessary to elucidate the basis of FMF in individual cases. The complete coding sequence for pyrin was analysed in representative patients in each of the five families, and all identified mutations were sought in each available family member, whether FMF symptoms were present or not.

MEFV mutations were identified in each of the five families: as pairs in four cases and as a solitary finding in one. All of the individuals with FMF in each of these three families carried the respective mutations, and no other mutations were identified despite obtaining the complete coding sequence of MEFV in each proband.

Two patients among these five kindreds had AA amyloidosis, the distribution and extent of which was confirmed by SAP scintigraphy. Identifiable visceral deposits were limited to the spleen and kidneys in both cases, and both had proteinuria as the sole clinical manifestation of their amyloid disease.

All of the individual point mutations in MEFV associated with dominant FMF have previously been recognized as solitary pathogenic mutations. The clinical features of FMF in these families were classical in every respect, including the response to colchicine. Familial Hibernian fever is due to mutations in the gene for tumour necrosis factor receptor 1, 13 and these were excluded in each of the three families by testing by Dr M.

This was the situation in two families reported here. 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.

Most centers, however, only test for a subset of the mutations that cause FMF, particularly those common in FMF patients. 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. National Library of Medicine.

Genetics Home Reference. Genes and Disease: Familial Mediterranean Fever. Colchicine prevents episodes from starting, but does not treat an episode that has already started. If the patient stops taking the medicine, episodes may return even after missing only one dose. If colchicine is taken regularly, the vast majority of children with FMF can live a normal life with a normal life expectancy. Do not change the medication dose without first discussing it with your doctor.

The most common side effects of colchicine are abdominal pain and diarrhea. If this occurs, the dose can be reduced until it is tolerated and then slowly increased back to the appropriate dose.

Reducing the intake of milk or other dairy products, or consuming lactose-free milk may help. Other side effects are nausea, vomiting, and abdominal cramps.

In rare cases, colchicine may cause muscle weakness, especially when taking antibiotics from the erythromycin macrolide family or statins cholesterol medications.

Therefore, these medications need to be given with caution with colchicine. The blood counts white and red blood cells and platelets may decrease occasionally and there may be mild elevations in liver enzymes, but these usually recover with dose reduction.

Children taking colchicine grow normally. Female patients do not have to stop taking colchicine during pregnancy or breast-feeding.

Children treated with colchicine should have blood and urine tests at least twice yearly. About ten percent of patients do not respond adequately or cannot tolerate colchicine. Recent research has found that medications that block interleukin-1, an important protein involved in the inflammatory process, may be effective for the majority of these patients.

These medications include rilonacept Arcalyst , anakinra Kineret , and canakinumab Ilaris. Complications can occur if familial Mediterranean fever isn't treated. Inflammation can lead to complications such as:. Mayo Clinic does not endorse companies or products.

Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Overview Familial Mediterranean fever FMF is a genetic autoinflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, chest and joints.

Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Ferri FF. Familial Mediterranean fever. In: Ferri's Clinical Advisor Elsevier;