Correspondence

Familial Mediterranean Fever — Amyloidosis and the Val726Ala Mutation

N Engl J Med 1998; 338:993-994April 2, 1998

Article

To the Editor:

Familial Mediterranean fever is an autosomal recessive disorder characterized by acute attacks of fever and inflammation of serous tissues. The disease affects certain ethnic groups, mainly Sephardic Jews, Armenians, Turks, and Arabs.1 Renal amyloidosis is the most severe complication and leads inevitably to chronic renal failure. Turks have severe disease with a relatively high incidence of amyloidosis as compared with other ethnic groups.2,3

Recently, the international and the French familial Mediterranean fever consortiums independently cloned the gene on the short arm of chromosome 16 and identified four ancient missense mutations on chromosomes of familial Mediterranean fever carriers in multiple ethnic groups.4,5 In its informative discussion the international consortium suggested that some of the phenotypic variation in the disease may be attributable to the difference between the Met694Val and Val726Ala mutations. The consortium suggested that the milder Val726Ala mutation is protective against amyloidosis and proposed that persons homozygous for Met694Val would be prone to amyloidosis but that Val726Ala homozygotes and compound heterozygotes would not.4

We describe four Turkish children with familial Mediterranean fever and renal amyloidosis, all of whom were heterozygous for Val726Ala. Mutation analysis was performed according to previous descriptions of restriction endonuclease analysis and the amplification-refractory mutation system.5 Table 1Table 1Characteristics of Four Patients with the Val726Ala Mutation. shows the clinical characteristics of the patients.

Our results show that renal amyloidosis can develop in patients with familial Mediterranean fever who are compound heterozygotes. These findings are important because regular prophylactic treatment with colchicine may prevent the development of amyloidosis.

Fatoş Yalçinkaya, M.D.
Nejat Akar, M.D.
Müge Misirlioğlu, Ph.D.
Ankara University Faculty of Medicine, 06100 Ankara, Turkey

5 References

1. 1

   Kastner DL. Intermittent and periodic arthritic syndromes. In: Koopman WJ, ed. Arthritis and allied conditions: a textbook of rheumatology. 13th ed. Vol. 1. Baltimore: Williams & Wilkins, 1997:1279-306.
   

2. 2

   Ozdemir AI, Sokmen C. Familial Mediterranean fever among the Turkish people. Am J Gastroenterol 1969;51:311-316
   Web of Science | Medline

3. 3

   Yalçinkaya F, Tümer N, Tekin M, Çakar N, Akçakuş M. Familial Mediterranean fever in Turkish children. In: Sohar E, Gafni J, Pras M, eds. Familial Mediterranean fever. London: Freund Publishing, 1997:157-61.
   

4. 4

   The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997;90:797-807
   CrossRef | Web of Science | Medline

5. 5

   The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31
   CrossRef | Web of Science | Medline

Citing Articles (21)

Citing Articles

1. 1

   Tekin Akpolat, Ozan Özkaya, Seza Özen. (2011) Homozygous M694V as a risk factor for amyloidosis in Turkish FMF patients. Gene
   CrossRef

2. 2

   Ayman El-Garf, Samia Salah, Iman Iskander, Hala Salah, Sherif Naseh Amin. (2010) MEFV mutations in Egyptian patients suffering from familial Mediterranean fever: analysis of 12 gene mutations. Rheumatology International 30:10, 1293-1298
   CrossRef

3. 3

   Fatih Albayrak, Nedim Yilmaz Selcuk, Ali R. Odabas, Ramazan Cetinkaya, Ibrahim Pirim. (2010) Genotype–Phenotype Correlation in Patients with Familial Mediterranean Fever in East Anatolia (Turkey). Genetic Testing and Molecular Biomarkers 14:3, 325-328
   CrossRef

4. 4

   Claudia Fonnesu, Claudia Cerquaglia, Maria Giovinale, Valentina Curigliano, Elena Verrecchia, Giuliana de Socio, Micaela La Regina, Giovanni Gasbarrini, Raffaele Manna. (2009) Familial Mediterranean Fever: A review for clinical management. Joint Bone Spine 76:3, 227-233
   CrossRef

5. 5

   Mohsen Esmaeili, Mortaza Bonyadi, Mandana Rafeey, Kazem Sakha, Mohammad Hossein Somi. (2008) Common MEFV Mutation Analysis in Iranian Azeri Turkish Patients with Familial Mediterranean Fever. Seminars in Arthritis and Rheumatism 37:5, 334-338
   CrossRef

6. 6

   Nuran Turkcapar, Timur Tuncalı, Sim Kutlay, Basak Yalcin Burhan, Gulay Kinikli, Sehsuvar Erturk, Murat Duman. (2007) The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever. Rheumatology International 27:6, 545-551
   CrossRef

7. 7

   F. Yalçınkaya, N. Çakar, B. Acar, E. Tutar, H. Güriz, A. H. Elhan, S. Öztürk, A. Kansu, E. İnce, S. Atalay, N. Girgin, Ü. Doğru, D. Aysev, M. Ekim. (2007) The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study. Rheumatology International 27:6, 517-522
   CrossRef

8. 8

   Onur Sakallioglu, Faysal Gok, Suleyman Kalman, Davut Gul, Erdal Gokcay. (2006) The phenotype–genotype correlations of FMF patients: a single center study. Rheumatology International 26:7, 638-640
   CrossRef

9. 9

   Fatos Onen. (2006) Familial Mediterranean fever. Rheumatology International 26:6, 489-496
   CrossRef

10. 10

    Vildan Ertekin, M. AySe SelimoGlu, Ibrahim Pirim. (2005) Familial Mediterranean fever in a childhood population in eastern Turkey. Pediatrics International 47:6, 640-644
    CrossRef

11. 11

    Hasan A. Majeed, Mohammed El-Khateeb, Hatem El-Shanti, Zaid Abu Rabaiha, Marwan Tayeh, Dana Najib. (2005) The Spectrum of Familial Mediterranean Fever Gene Mutations in Arabs: Report of a Large Series. Seminars in Arthritis and Rheumatism 34:6, 813-818
    CrossRef

12. 12

    (2005) Familial Mediterranean Fever (FMF) in Turkey. Medicine 84:1, 1-11
    CrossRef

13. 13

    Nejat Akar, Metis Hasipek, Ece Akar, Mesiha Ekim, Fatos Yatçinkaya, Nilgün Clakar. (2003) Serum amyloid A1 and tumor necrosis factor-alpha alleles in Turkish Familial Mediterranean Fever patients with and without amyloidosis. Amyloid 10:1, 12-16
    CrossRef

14. 14

    Cecile Cazeneuve, Hasmik Ajrapetyan, Stephanie Papin, Francoise Roudot‐Thoraval, David Genevieve, Elizaveta Mndjoyan, Marina Papazian, Ashot Sarkisian, Ara Babloyan, Brigitte Boissier, Philippe Duquesnoy, Jean‐Claude Kouyoumdjian, Emmanuelle Girodon‐Boulandet, Gilles Grateau, Tamara Sarkisian, Serge Amselem. (2000) Identification of MEFV ‐Independent Modifying Genetic Factors for Familial Mediterranean Fever. The American Journal of Human Genetics 67:5, 1136-1143
    CrossRef

15. 15

    Mustafa Tekin, Fatoş Yalçinkaya, Nilgün Çakar, Nejat Akar, Müge Mısırlıoğlu, Hakkı Taştan, Necmiye Tümer. (2000) MEFV mutations in multiplex families with familial Mediterranean fever: is a particular genotype necessary for amyloidosis?. Clinical Genetics 57:6, 430-434
    CrossRef

16. 16

    Gilles Grateau. (2000) The relation between familial Mediterranean fever and amyloidosis. Current Opinion in Rheumatology 12:1, 61-64
    CrossRef

17. 17

    Jens Rengelshausen, Michael Rünzi, Ali Canbay, Guido Gerken, Thomas Philipp. (1999) Familiäres Mittelmeerfieber. Medizinische Klinik 94:12, 685-689
    CrossRef

18. 18

    Avi Livneh, Pnina Langevitz, Yael Shinar, Nurit Zaks, Daniel L. Kastner, Mordechai Pras, Elon Pras. (1999) MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid 6:1, 1-6
    CrossRef

19. 19

    (1999) MEFV mutation analysis in Turkish familial Mediterranean fever patients with amyloidosis. Amyloid 6:4, 301-302
    CrossRef

20. 20

    Jonathan Samuels, Ivona Aksentijevich, Yelizaveta Torosyan, Michael Centola, Zuoming Deng, Raman Sood, Daniel L. Kastner. (1998) Familial Mediterranean Fever at the Millennium. Medicine 77:4, 268-297
    CrossRef

21. 21

    Xavier Bosch, Mónica Pomares. (1998) Familial Mediterranean fever. The Lancet 351:9116, 1658
    CrossRef