Investigation of the Relationship Between Disease Severity and Development of Amyloidosis and Genetic Mutation in FMF Disease

Overview

Journal Ir J Med Sci

Specialty General Medicine

Date 2022 Aug 16

PMID 35972675

Authors

Berk Bas

Hayriye Sayarlioglu

Zeliha Yarar

Melda Dilek

Nurol Arik

Mehmet Sayarlioglu

Affiliations

Soon will be listed here.

Abstract

Background: Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease. Amyloidosis is the most important complication of FMF that determines the prognosis of the disease.

Aims: In our study, we have investigated the relationship between the genetic mutations with the disease severity and the frequency of development of amyloidosis inpatients with FMF.

Methods: A total of 148 patients with FMF were included this study. The relationship between disease activity score, clinical findings, response to treatment, and presence of amyloid and genetic mutations were evaluated.

Results: One hundred forty-eight patients (80 women (54%), 68 men (46%)) were enrolled over 18 years of age. The mean age of the patients was 30.98 ± 11.18 (18-67) years. In our study, the most frequently seen mutations are M694V, M680I, R202Q, and E148Q, respectively. The most common genotype is M694V/M694V mutation and this mutation has been found in 37 patients (25%). In 25 patients, M694V heterozygous have been found (16.8%). The third frequent mutationis M694V/M680I/R202Q has been found in13 patients (8.7%). In 23 patients, amyloidosis has been developed. Ten patients with amyloidosis have M694V homozygous mutations (27%) and 5 patients with amyloidosis M694V heterozygous (20%) mutations. The both of the two patients who carry the homozygous E148Q mutations have developed amyloidosis.

Conclusions: In our study, the distribution of the frequency of mutations is consistent with other similar studies performed in Turkey. We found that patients with M694V mutation had a significantly higher rate of exacerbation, higher drug doses for treatment, and a close relationship with amyloidosis, as compared to patients with other mutations.

Citing Articles

Relationship between sacroiliitis and inflammatory markers in familial Mediterranean fever.

Atik I, Atik S Rev Assoc Med Bras (1992). 2024; 70(5):e20240068.

PMID: 38775516 PMC: 11111121. DOI: 10.1590/1806-9282.20240068.

Optimized Treatment of Interleukin (IL-1)-Mediated Autoinflammatory Diseases: Impact of Disease Activity-Based Treatment Adjustments.

Welzel T, Zapf B, Klotsche J, Satirer O, Benseler S, Kuemmerle-Deschner J J Clin Med. 2024; 13(8).

PMID: 38673592 PMC: 11050771. DOI: 10.3390/jcm13082319.

Pan-Immune-Inflammation Value Could Be a New Marker to Predict Amyloidosis and Disease Severity in Familial Mediterranean Fever.

Ocak T, Gorunen A, Coskun B, Yagiz B, Sag S, Ocakoglu G Diagnostics (Basel). 2024; 14(6).

PMID: 38535054 PMC: 10968919. DOI: 10.3390/diagnostics14060634.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Kilic Konte E, Haslak F, Yildiz M, Gucuyener N, Ulkersoy I, Gunalp A Eur J Pediatr. 2023; 182(12):5473-5482.

PMID: 37777601 DOI: 10.1007/s00431-023-05209-4.

References

Ben-Chetrit E, Touitou I . Familial mediterranean Fever in the world. Arthritis Rheum. 2009; 61(10):1447-53. DOI: 10.1002/art.24458. View

Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N . Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet. 2001; 9(7):553-5. DOI: 10.1038/sj.ejhg.5200674. View

Pras E, Aksentijevich I, Gruberg L, Balow Jr J, Prosen L, Dean M . Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16. N Engl J Med. 1992; 326(23):1509-13. DOI: 10.1056/NEJM199206043262301. View

Levy E, Shen Y, Kupelian A, Kruglyak L, Aksentijevich I, Pras E . Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246. Am J Hum Genet. 1996; 58(3):523-34. PMC: 1914560. View

Touitou I . The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet. 2001; 9(7):473-83. DOI: 10.1038/sj.ejhg.5200658. View

Livneh A, Balow Jr J, Pras E, Kastner D, Pras M, Langevitz P . Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998; 75(2):216-9. DOI: 10.1002/(sici)1096-8628(19980113)75:2<216::aid-ajmg20>3.0.co;2-r. View

Mattit H, Joma M, Al-Cheikh S, El-Khateeb M, Medlej-Hashim M, Salem N . Familial Mediterranean fever in the Syrian population: gene mutation frequencies, carrier rates and phenotype-genotype correlation. Eur J Med Genet. 2006; 49(6):481-6. DOI: 10.1016/j.ejmg.2006.03.002. View

Nursal A, Tekcan A, Kaya S, Turkmen E, Yigit S . Mutational Spectrum of the MEFV Gene in AA Amyloidosis Associated With Familial Mediterranean Fever. Iran J Kidney Dis. 2016; 10(3):107-12. View

Booty M, Chae J, Masters S, Remmers E, Barham B, Le J . Familial Mediterranean fever with a single MEFV mutation: where is the second hit?. Arthritis Rheum. 2009; 60(6):1851-61. PMC: 2753538. DOI: 10.1002/art.24569. View

10.

Akar N, Misiroglu M, Yalcinkaya F, Akar E, Cakar N, Tumer N . MEFV mutations in Turkish patients suffering from Familial Mediterranean Fever. Hum Mutat. 1999; 15(1):118-9. DOI: 10.1002/(SICI)1098-1004(200001)15:1<118::AID-HUMU29>3.0.CO;2-5. View

11.

Gershoni-Baruch R, Brik R, Shinawi M, Livneh A . The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever. Eur J Hum Genet. 2002; 10(2):145-9. DOI: 10.1038/sj.ejhg.5200776. View

12.

Kasifoglu T, Yasar Bilge S, Sari I, Solmaz D, Senel S, Emmungil H . Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study. Rheumatology (Oxford). 2013; 53(4):741-5. DOI: 10.1093/rheumatology/ket400. View

13.

Touitou I, Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D . Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum. 2007; 56(5):1706-12. DOI: 10.1002/art.22507. View

14.

Gedalia A, Adar A, Gorodischer R . Familial Mediterranean fever in children. J Rheumatol Suppl. 1992; 35:1-9. View