to the editor: Dr. Wattendorf and Mr. Hadley err in their article “Family History: The Three-Generation Pedigree,”1 when they state that persons of Ashkenazi Jewish origin (Jews of Eastern European ancestry) “share odds of one in four for carrying a defective gene for familial Mediterranean fever.”1 Not only are their statistics improbable, but they have the wrong ethnicity, as this is an affliction of Sephardi (Spanish) and Oriental Jews, as well as Middle Eastern Arabs. Familial Mediterranean fever is most commonly found in the Jews of Libya, with an incidence of one out of 600 persons in this population, in contrast to the Ashkenazi occurrence of one out of 3,000 to one out of 5,000.2
in reply: Familial Mediterranean fever (FMF) is a disorder characterized by recurring fevers and symptoms of localized inflammation, often abdominal pain or arthritis. Diagnosis is important because effective treatment with colchicine reduces FMF attacks as well as prevents the chronic complication of amyloidosis.1 A young patient presenting with fever after immunization, or periodic fevers and abdominal pain, is often a diagnostic challenge. Consideration of FMF in the differential diagnosis is aided by an important aspect of family history collection—documenting the most specific information about ancestral origin as possible. In our article, as originally submitted for publication, we stated, “Those of Armenian, Turkish, Arabic, and Sephardic Jewish origin share odds of one in eight for carrying a defective gene for familial Mediterranean fever. In these patients, awareness of their disease risk is important because early diagnosis avoids prolonged evaluation for other disorders and makes effective treatment possible.”2
A recent review3 of the literature finds the carrier frequency of FMF in Mediterranean and Middle Eastern populations to be as high as one in three to one in five.1 In one study,4 persons of Ashkenazi Jewish or Muslim Arabic origin share approximate odds of one in four (1:4.5 and 1:4.3, respectively) for carrying a defective gene for FMF. This is a remarkably high frequency of carrier status. The most prevalent mutation found in Ashkenazi Jews with FMF (E148Q of the MEFV gene), when identified in the homozygous state (both copies) or in combination with most other mutations, often results in a benign condition.
The very high carrier frequencies of specific mutations in the same gene among communities with an eastern Mediterranean ancestry have been suggested to confer resistance to disease historically endemic to this area. Cultural, social, or religious affiliation as defined by “ethnicity” may be difficult to interpret; however, documenting the most precise detailed ancestry an individual can provide is a useful clinical tool and should be included in every family history.