Familial Mediterranean fever in heterozygotes: are we able to accurately diagnose the disease in very young children?

Objective: Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disease due to mutations in MEFV. Descriptions of disease manifestations among patients carrying a single mutated MEFV allele are becoming more frequent, although no data are available on the long-term outcome. We undertook this study to assess the accuracy of clinical diagnosis in children carrying a single mutated MEFV allele with symptoms of recurrent autoinflammatory disorder.

Methods: We performed a retrospective single-center study of 33 patients with autoinflammatory disorders age <6 years at disease onset with 1 mutated MEFV allele. The phenotype of the patients was investigated in detail, and the clinical picture and outcome of 18 patients with an initial FMF diagnosis according to current clinical criteria were compared to those of 25 homozygous or compound heterozygous FMF patients.

Results: No major differences in presenting signs or initial response to colchicine were observed between patient groups. During followup, heterozygotes had a milder disease course compared to homozygotes and were less prone than homozygotes to experience new clinical signs of FMF. At puberty, clinical signs of FMF completely disappeared in 5 of 18 heterozygotes, allowing them to discontinue colchicine without recurrence of symptoms or increases in inflammatory marker levels.

Conclusion: Our data suggest that the clinical diagnosis of FMF in very young heterozygous children should be made with caution. At this young age they can present with an FMF-like disease-similar to that seen in patients carrying 2 mutated alleles-that is not necessarily predictive of life-long illness.