The presence of M694V was found to be associated with more severe course of FMF, earlier age of onset and more frequent arthritis in the Syrian children with FMF compared to other FMF patients who do not have this mutation.
FMF patients heterozygous for E148Q mutation, heterozygous for M694I mutation, or combined heterozygous for E148Q and M694I mutations, which were found to be major mutations in an FMF study group in Japan, suffer from arthritis, the severity of which is likely to be lower than in FMF patients with M694V mutations.
Fever and arthritis were determined in similar ratios to other genotypes (76% and 19%, respectively) in the M694V/M694V genotype (74% and 29%, respectively) (p > 0.50 and p > 0.20, respectively).
Logistic regression analysis showed that homozygosity for the M694V allele (odds ratio [OR] 4.27, 95% confidence interval [95% CI] 2.01-9.07), the presence of the SAAalpha/alpha genotype (OR 2.99, 95% CI 1.47-6.09), the occurrence of arthritis attacks (OR 2.43, 95% CI 1.17-5.06), and male sex (OR 1.73, 95% CI 0.90-3.33) were significantly and independently associated with renal amyloidosis.
The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively).
The presence of a homozygous M694V mutation was significantly associated with a more severe form of the disease: the clinical onset of the disease manifested at an earlier age; the number of attacks per month was higher; the global assessment by the treating physician and the severity of pain scored higher; and arthritis was more frequent.
Their parents were heterozygous for the same mutation p.M680I, however, the mother showed severe symptoms of FMF (recurrent attacks of fever, arthralgia and arthritis, abdominal pain, thoracic pain), the father showed recurrent pustulosis prevalent on the hands and limbs, with arthralgia and abdominal pain.
Although four of the 26 patients with E148Q/E148Q were asymptomatic at the time of evaluation, abdominal pain was seen in 77% of the patients, fever in 66%, arthralgia in 50%, arthritis in 15.4%, and vomiting in 23.8%.