Genotype Mutations in Palestinian Children with Familial Mediterranean Fever: Clinical Profile, and Response to Colchicine Treatment: A Retrospective Cohort Study

Abstract

Background: Familial Mediterranean fever is a hereditary autoinflammatory disease affecting mainly Arabs, Turks, Armenians, and Jews with genotype-phenotype heterogeneity, presenting as recurrent episodes of fever along with polyserositis and rash. To date, more than 370 mutations in the MEFV gene have been recognized to cause the disease. Methods: We conducted a retrospective cohort study involving 124 patients in Hebron, Palestine, diagnosed with FMF at the Al-Ahli, and Palestinian Red Crescent Society (PRCS) Hospitals. Results: The median age of diagnosis was five years, presenting as abdominal pain (76.6%), fever (67.7%), joint pain and arthritis. Regarding MEFV gene mutations, we had 62 patients (50%) with heterozygous genotypes, 40 patients (32.3%) with homozygous phenotypes, 21 patients (16.9%) with compound heterozygous genotypes, and one was a missing state. Regarding variant frequencies, M694V was the most common one (43.4%), followed by E148Q (15.6%), V726A (5.7%), A744S (4.1%), and R202Q (4.1%). Positive family history was detected in 59 patients (54.6%), and there was no significant difference in zygosity regarding characteristics, consanguinity, and family history. Conclusions: We affirm in this study of 124 children with FMF, abdominal pain, followed by fever, joint pain and arthritis were the main manifestations. Further, M694V, E148Q, V726A, A744S, and R202Q were the most frequent mutations, and carrying the M649V mutations is associated with a predisposition to other comorbidities. We believe that this study gives a pervasive overview of FMF in Palestinian patients. Looking forward, future studies on a larger number of patients could precisely highlight the genotype-phenotype association among FMF patients.