Familial Mediterranean Fever — Amyloidosis and the Val726Ala Mutation

Abstract

Familial Mediterranean fever is an autosomal recessive disorder characterized by acute attacks of fever and inflammation of serous tissues. The disease affects certain ethnic groups, mainly Sephardic Jews, Armenians, Turks, and Arabs.1 Renal amyloidosis is the most severe complication and leads inevitably to chronic renal failure. Turks have severe disease with a relatively high incidence of amyloidosis as compared with other ethnic groups.2,3 Recently, the international and the French familial Mediterranean fever consortiums independently cloned the gene on the short arm of chromosome 16 and identified four ancient missense mutations on chromosomes of familial Mediterranean fever carriers in multiple ethnic groups.4,5 In its informative discussion the international consortium suggested that some of the phenotypic variation in the disease may be attributable to the difference between the Met694Val and Val726Ala mutations. The consortium suggested that the milder Val726Ala mutation is protective against amyloidosis and proposed that persons homozygous for Met694Val would be prone to amyloidosis but that Val726Ala homozygotes and compound heterozygotes would not.4 We describe four Turkish children with familial Mediterranean fever and renal amyloidosis, all of whom were heterozygous for Val726Ala. Mutation analysis was performed according to previous descriptions of restriction endonuclease analysis and the amplification-refractory mutation system.5 Table 1Table 1 Characteristics of Four Patients with the Val726Ala Mutation. shows the clinical characteristics of the patients. Our results show that renal amyloidosis can develop in patients with familial Mediterranean fever who are compound heterozygotes. These findings are important because regular prophylactic treatment with colchicine may prevent the development of amyloidosis.