Tomer Maller1, Ilan Ben-Zvi1,2,3,4,5, Merav Lidar2,3,4, Avi Livneh6,7,8,9. 1. Medicine F, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 2. FMF Clinic, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 3. Rheumatology Unit, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 4. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. The Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 6. Medicine F, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. prof.livneh@gmail.com. 7. FMF Clinic, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. prof.livneh@gmail.com. 8. Rheumatology Unit, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. prof.livneh@gmail.com. 9. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. prof.livneh@gmail.com.
Abstract
BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease associated with mutations in the Mediterranean fever gene (MEFV) that manifests with recurrent episodes of febrile serositis. Fabry's disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A gene and presents with a wide range of gastrointestinal, skin, vascular, renal and neurological manifestations. FMF and FD share similar manifestations, which may lead to misdiagnosis of one as the other; mostly FD is misdiagnosed as FMF. Moreover, various overlapping manifestations may stem from comorbidities, commonly coupled to FMF (such as Behcet's disease, inflammatory bowel disease, glomerulonephritis, fibromyalgia, and multiple sclerosis), as well as from colchicine adverse effects, which may add to the diagnostic confusion. Thus, we postulated that screening FMF for FD will lead to the identification of patients falsely diagnosed with FMF or who, in addition to FMF, suffer from FD that was previously missed. METHODS: To identify missed FD among the FMF population, we performed chemical and genetic analyses for FD in blood samples obtained from a cohort of FMF patients followed in the specialized FMF center of our institution. To increase the likelihood of detecting patients with FD, we enriched the surveyed FMF population with patients exhibiting manifestations shared by patients with FD or who deviate from the typical FMF presentation. RESULTS AND CONCLUSIONS: Of 172 surveyed FMF patients in a cohort derived from a clinic dedicated to FMF, none had FD. Thus, the postulation of increased odds for detecting FD in patients with FMF was not confirmed. Further exploration for FD in FMF population, is nevertheless recommended.
BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease associated with mutations in the Mediterranean fever gene (MEFV) that manifests with recurrent episodes of febrile serositis. Fabry's disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A gene and presents with a wide range of gastrointestinal, skin, vascular, renal and neurological manifestations. FMF and FD share similar manifestations, which may lead to misdiagnosis of one as the other; mostly FD is misdiagnosed as FMF. Moreover, various overlapping manifestations may stem from comorbidities, commonly coupled to FMF (such as Behcet's disease, inflammatory bowel disease, glomerulonephritis, fibromyalgia, and multiple sclerosis), as well as from colchicine adverse effects, which may add to the diagnostic confusion. Thus, we postulated that screening FMF for FD will lead to the identification of patients falsely diagnosed with FMF or who, in addition to FMF, suffer from FD that was previously missed. METHODS: To identify missed FD among the FMF population, we performed chemical and genetic analyses for FD in blood samples obtained from a cohort of FMF patients followed in the specialized FMF center of our institution. To increase the likelihood of detecting patients with FD, we enriched the surveyed FMF population with patients exhibiting manifestations shared by patients with FD or who deviate from the typical FMF presentation. RESULTS AND CONCLUSIONS: Of 172 surveyed FMF patients in a cohort derived from a clinic dedicated to FMF, none had FD. Thus, the postulation of increased odds for detecting FD in patients with FMF was not confirmed. Further exploration for FD in FMF population, is nevertheless recommended.