Familial Mediterranean Fever in the first two years of life: a unique phenotype of disease in evolution.
OBJECTIVE
To characterize the clinical and genetic features of familial Mediterranean fever (FMF).


METHODS
Clinical presentation and MEditerranean FeVer mutation type of all patients with FMF, who first manifested the disease at < or =2 years of age were analyzed and compared with patients who first presented with FMF between 2 and 16 years.


RESULTS
Of 814 patients with FMF, in 254 patients (31.2%) the first FMF attack was at < or =2 years of age, with a mean age at onset of 1.1 +/- 0.8 years. They were compared with 242 patients who presented with their first manifestation of FMF at 2 to 16 years. The clinical manifestations of FMF were comparable in the 2 patient groups, but the delay of diagnosis was longer in patients with early presentation (3.2 +/- 3.2 years vs.1.9 +/- 2.7 years in the group with onset at 2-16 years, P < .001). A subgroup of patients (60/254), who were diagnosed at < or =2 years had the highest rate of attacks of fever alone as their sole manifestation (40.0% vs 8.4%, P < .05), and less peritonitis (45% vs 86.1%, P < .05) and pleuritis (3.4% vs 32.9%, P < .05). Most of these patients were homozygous for the M694V mutation and were of North African (Sephardic Jewish) extraction.


CONCLUSIONS
In early life, FMF often begins with an atypical presentation, characterized by attacks of fever alone, and its diagnosis and initiation of treatment is therefore significantly delayed.
Department of Pediatrics A, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel. Electronic address: Shay.pade@sheba.health.gov.il.
Shai
S
Padeh
Department of Medicine F and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
Avi
A
Livneh
Genetic Institute, Sheba Medical Center, Tel Hashomer, Israel.
Elon
E
Pras
Department of Medicine F and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
Yael
Y
Shinar
Department of Medicine F and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
Merav
M
Lidar
Department of Medicine F and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
Olga
O
Feld
Department of Pediatrics A, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
Yackov
Y
Berkun
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D000071198:Pyrin
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin