Background/Purpose: In 1945, Dr. Sheppard Siegel, a Mount Sinai allergist, described 5 patients with “Benign Paroxysmal Peritonitis,” a disorder now recognized as Familial Mediterranean Fever (FMF). By 1964 (Am J Med 36: 893, 1964), he was able to review a cumulative experience with 50 patients affected by this disorder from the New York City area, describing in detail self-limited attacks of intense abdominal pain with accompanying fever, usually found in younger patients of specific ethnicities, including 38 ashkenazi and 4 sephardic jews, and 7 armenians . Possibly affected by the disorder himself, he also identified “progressive nephropathy” as a feared complication, and correctly surmised an underlying genetic cause. Although Dr Siegel was unable to identify an effective treatment, including a search for food allergies, his work overlapped with that of Dr Tsai Fan Yu @ Mount Sinai 1962-86 that established the efficacy of daily colchicine prophylaxis for gout, eventually identified as another autoinflammatory disease. In 1997 FMF was linked to the MEFV gene on chromosome 16 by two groups, and, that year, we established an referral practice for FMF and Amyloidosis at the Mount Sinai Medical center. 

Methods: We now report our experience with 51 patients affected by this disease, and /or found to have MEFV mutation over the period 1997-2015. 

Results:   In our cohort, the most common ethnicity was Sephardic Jewish (17), with varying origins from Morocco (4) to Khazakhstan, and the most common genotype was heterozygous M694V (22%). 9 patients were homozygous, 17 patients were heterozygous, and 10 patients were compound heterozygous. An additional three patients having the typical FMF phenotype (Tel Hashomer criteria) and response to colchicine were wild type, assessed by full DNA sequence analysis. Interestingly, a number of patients with the FMF phenotype and documented MEFV mutations began manifesting symptoms in adulthood; atypical phenotypes seen were periodic fever without serositis, recurrent pleuritis, and recurrent pericarditis. Associated diseases were nonspecific colitis, thalassemia, G6PD deficiency, and one case of primary Sjogren ’s syndrome complicated by mesothelioma. Only one patient with typical FMF symptoms eventually developed secondary (AA) amyloidosis. However, one patient homozygous for the M694V mutation had secondary amyloidosis as his initial manifestation of the disease (“phenotype II”), and four additional patients with secondary amyloidosis, and one egyptian man  with renal amyloid due to Lect2, were found to have the low penetrance E148Q mutation. Median delay from first attack to diagnosis was 10 years. Treatment modalities included colchicine and anticytokines, notably IL-1 and more recently IL-6 antagonists. 

Conclusion:

Availability of genetic testing has allowed analysis of  the heterogeneity of genotype-phenotype correlations and distribution frequencies for pyrin mutations in a “melting pot” population from which the initial description of FMF in New York City were made.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pyrin-mefv-mutations-in-new-york-revisiting-the-mount-sinai-experience-with-periodic-fever-and-serositis/