FMF is an inherited autoinflammatory syndrome, characterized by attacks of painful periodic fever caused by diffuse serositis and risk of secondary amyloidosis due to IL-1β-mediated inflammation.
The late onset, often atypical and mild clinical manifestations and absence of AA amyloidosis in our patients might be related to low-penetrance and heterozygous MEFV variants.
AA amyloidosis was diagnosed in 17 (68 %) of 25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene mutations.
To investigate the association between CD14 promotor C-159T polymorphism and development of amyloidosis, one hundred and forty-six patients who had FMF and had not developed amyloidosis; 26 with FMF and secondary amyloidosis and 92 controls were genotyped at the CD14-C159T locus.
Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.
A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFVH478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?
The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.
The association of pyrin Q148 with AA amyloidosis and with obscure chronic inflammatory diseases suggests the variant may augment inflammation non-specifically, which might have been beneficial during evolution, but could potentially exacerbate many chronic inflammatory disorders.
We describe a case of amyloid goiter revealing a systemic amyloidosis secondary to familial Mediterranean fever (FMF) with homozygous MEFV mutation, and we review the literature.