A Japanese Patient with Familial Mediterranean Fever Associated with Compound Heterozygosity for Pyrin Variant E148Q/M694I

Abstract

Familial Mediterranean fever (FMF) is an inherited inflammatory disease occurring mainly in Mediterranean and Middle Eastern populations. FMF is caused by mutations in the MEFV gene that encodes pyrin/marenostrin. Here, we report a Japanese female FMF patient with heterozygosity for the compound pyrin E148Q/M694I showing recurrent fever, serositis or delay in skin wound healing. Her father and elder sister were heterozygous for pyrin variant M694I alone and sometimes suffered from mild fever or delay in wound healing, but her mother was heterozygous for pyrin variant E148Q alone and had no symptoms. This suggested that the inheritance of FMF occurred not only in an autosomal recessive manner but also in an autosomal dominant manner in this Japanese family, and the severity of the disease differed among the family members in relation to the mutation. In the treatment of FMF, colchicine, reserpine or prazosin hydrochloride have been reported to prevent the attacks, but, in our patient such drugs were ineffective or caused side effects, and only the anti-allergic drug azelastine was of benefit in relieving the attacks. (Internal Medicine 44: 261-265, 2005)

Familial Mediterranean Fever with Onset at 66 Years of Age

“…The E148Q mutation is considered to be the mildest mutation and to result in a milder form of FMF (19). It has also been reported that patients with homozygosity for the pyrin variant E148Q mutation have less severe symptoms and fewer attacks than those with heterozygosity for the pyrin variant E148Q/M694I mutation (15,16). The patient in the present case was found to have a heterozygous E148Q mutation.…”

An Atypical Familial Mediterranean Fever Patient Who Developed Ulcers in the Terminal Ileum and Recurrent Abscess-like Lesions in Multiple Organs

“…FMF is observed most frequently in Jewish, Armenian, Arab, Turkish, and Italian people, and it has been thought to be a rare disease in Japan. However, an increasing number of cases of FMF have been reported in Japan (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Unlike typical FMF cases in endemic areas, some cases in Japan have been sporadic and adult-onset cases.…”

Hereditary Periodic Fever Syndromes in Japan

“…In this issue, Nakamura et al report a 34-year-old Japanese female FMF patient with heterozygous E148Q/M694I mutation (15). Interestingly, E148Q heterozygous mutation seems to enhance the FMF clinical symptoms of M694I heterozygous phenotype in her pedigree analysis (15).…”

“…Many other drugs for FMF, such as interferon alpha, thalidomide, reserpine, prazosin hydrochloride (20), and herbal medicine (19) have been reported to date (8). Because of the side effects, Nakamura et al tried to use azelastine, an anti-allergic drug in this patient rather than colchicine, and azelastine successfully reduced the frequency and degree of the attacks (15). As it is similar to colchicine in function in that it inhibits neutrophil chemotaxis and has less adverse effects, azelastine may be one of the promising drugs for FMF.…”

“…Although a few cases were diagnosed by MEFV gene analysis, there has been a proliferation of individual FMF case reports from Japan (9)(10)(11)(12)(13)(14). In this issue, Nakamura et al report a 34-year-old Japanese female FMF patient with heterozygous E148Q/M694I mutation (15). Interestingly, E148Q heterozygous mutation seems to enhance the FMF clinical symptoms of M694I heterozygous phenotype in her pedigree analysis (15).…”