Yıl: 2022 Cilt: 28 Sayı: 2 Sayfa Aralığı: 97 - 101 Metin Dili: İngilizce DOI: 10.4274/tnd.2022.26780 İndeks Tarihi: 28-05-2023

Diagnostic Delay and Clinical Features in Friedreich’s Ataxia

Öz:
Objective: Friedreich ataxia (FRDA) is the most frequent hereditary ataxia characterized by progressive gait and limb ataxia, dysarthria, sensory loss, and muscular weakness. Due to insufficient awareness of patients and their relatives, poor knowledge of healthcare professionals, and difficulty in accessing diagnostic tests, delay in diagnosis is seen in many diseases, especially in rare diseases. In this study, the diagnostic delay, and clinical features of individuals with FRDA were investigated. Materials and Methods: Individuals who fulfilled the criteria for Harding clinical diagnosis and who had increased GAA repetition in the genetic examination were included in the study. Demographic and clinical data of the patients such as initial symptoms, age at symptom onset, time from the onset of symptoms to the diagnosis, and comorbid conditions were recorded. In addition, detailed neurological examinations of the patients were made, and they were evaluated with the scale for the assessment and rating of ataxia (SARA). Results: A total of 22 patients, 12 males, and 10 females, were included in the study. The mean age of the individuals was 30.4±6.3 (19-41). Age of symptom onset was 19±5.6 (9-32), age at diagnosis was 22.1±6.1 (13-33), and the time from onset of symptoms to diagnosis was 3.03±2.66 (0.2-9) years. While the first symptom of 19 patients (86.4%) was trunk ataxia, the first symptom of 3 patients (13.6%) was extremity ataxia. Eight (36.4%) patients were non-ambulatory and 14 (63.6%) were ambulatory. The mean total SARA score was 18.2±6.7 [median 19.5 (7-30)]. Conclusion: This study is the first study to evaluate the diagnosis delay in patients with FRDA in our country. Although FRDA was the most common hereditary ataxia, in our study, it was shown that there was a significant delay in diagnosis in patients with FRDA. There is a need for studies that will raise awareness of public and health professionals about FRDA.
Anahtar Kelime:

Friedreich Ataksisinde Tanı Gecikmesi ve Klinik Özellikler

Öz:
Amaç: Friedreich ataksisi (FRDA) progresif yürüyüş ve ekstremite ataksisi, dizartri, duyu kaybı ve kas güçsüzlüğü ile karakterize en sık kalıtsal ataksidir. Birçok hastalıkta, özellikle nadir hastalıklarda; hasta ve hasta yakınlarının yetersiz farkındalığı, sağlık uzmanlarının bilgi birikiminin yeterli olmaması ve tanı testlerine erişmekte güçlük nedeniyle tanı gecikmesi görülür. Bu çalışmada, FRDA’lı bireylerin tanı gecikmesi ve klinik özellikleri araştırılmıştır. Gereç ve Yöntem: Harding klinik tanı kriterlerini karşılayan ve genetik incelemede artmış GAA trinükleotid tekrarı olan bireyler çalışmaya alınmıştır. Hastaların başlangıç semptomları, semptom başlangıç yaşı, semptom başlangıcından tanıya kadar geçen süre ve komorbid durumlar gibi demografik ve klinik verileri kaydedilmiştir. Ayrıca hastaların detaylı nörolojik muayeneleri yapılmış ve ataksi değerlendirme ve derecelendirme skalası (SARA) ile kaydedilmiştir. Bulgular: Çalışmaya 12 erkek ve 10 kadın olmak üzere toplam 22 hasta dahil edildi. Bireylerin yaş ortalaması 30,4±6,3 (19-41) idi. Semptom başlangıç yaşı 19±5,6 (9-32), tanı yaşı 22,1±6,1 (13-33) ve semptomların başlamasından tanıya kadar geçen süre 3,03±2,66 (0,2-9) yıl idi. On dokuz olgunun ilk belirtisi (%86,4) gövde ataksisi iken, 3 olgunun (%13,6) ilk belirtisi ekstremite ataksisi idi. Sekiz (%36,4) olgu ambulatuvar iken 14 (%63,6) olgu non-ambulatuvar idi. Ortalama toplam SARA skoru 18,2±6,7 idi [medyan 19,5 (7-30)]. Sonuç: Bu çalışma ülkemizde FRDA hastalarında tanı gecikmesini değerlendiren ilk çalışmadır. Her ne kadar FRDA en sık kalıtsal ataksi olsa da, çalışmamızda FRDA’lı hastalarda tanıda önemli bir gecikme olduğu gösterilmiştir. Toplumun ve sağlık profesyonellerinin FRDA konusunda farkındalıklarını artıracak çalışmalara ihtiyaç vardır.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Delatycki MB, Bidichandani SI. Friedreich ataxia- pathogenesis and implications for therapies. Neurobiol Dis 2019;132:104606.
  • 2. Galea CA, Huq A, Lockhart PJ, et al. Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia. Ann Neurol 2016;79:485-495.
  • 3. Schulz JB, Boesch S, Bürk K, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol 2009;5:222-234.
  • 4. Nachun D, Gao F, Isaacs C, et al. Peripheral blood gene expression reveals an inflammatory transcriptomic signature in Friedreich's ataxia patients. Hum Mol Genet 2018;27:2965-2977.
  • 5. Cook A, Giunti P. Friedreich's ataxia: clinical features, pathogenesis and management. Br Med Bull 2017;124:19-30.
  • 6. Tsou AY, Paulsen EK, Lagedrost SJ, et al. Mortality in Friedreich ataxia. J Neurol Sci 2011;307:46-49.
  • 7. Sarva H, Shanker VL. Treatment options in degenerative cerebellar ataxia: a systematic review. Mov Disord Clin Pract 2014;1:291-298.
  • 8. Yetkin MF, Gültekin M. Efficacy and tolerability of interferon gamma in treatment of Friedreich's ataxia: retrospective study. Noro Psikiyatr Ars 2020;57:270-273.
  • 9. Tomassini B, Arcuri G, Fortuni S, et al. Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model. Hum Mol Genet 2012;21:2855-2861.
  • 10. Pogue RE, Cavalcanti DP, Shanker S, et al. Rare genetic diseases: update on diagnosis, treatment and online resources. Drug Discov Today 2018;23:187- 195.
  • 11. Shook SJ, Pioro EP. Racing against the clock: recognizing, differentiating, diagnosing, and referring the amyotrophic lateral sclerosis patient. Ann Neurol 2009;65(Suppl 1):S10-S16.
  • 12. Campos MA, Alazemi S, Zhang G, et al. Clinical characteristics of subjects with symptoms of alpha1-antitrypsin deficiency older than 60 years. Chest 2009;135:600-608.
  • 13. Pierucci P, Lenato GM, Suppressa P, et al. A long diagnostic delay in patients with hereditary haemorrhagic telangiectasia: a questionnaire-based retrospective study. Orphanet J Rare Dis 2012;7:33.
  • 14. Harding AE. Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 1981;104:589-620.
  • 15. Marelli C, Figoni J, Charles P, et al. Annual change in Friedreich's ataxia evaluated by the scale for the assessment and rating of ataxia (SARA) is independent of disease severity. Mov Disord 2012;27:135-138.
  • 16. Reetz K, Dogan I, Costa AS, et al. Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data. Lancet Neurol 2015;14:174-182.
  • 17. Stephenson J, Zesiewicz T, Gooch C, et al. Gait and balance in adults with Friedreich's ataxia. Gait Posture 2015;41:603-607.
  • 18. The voice of 12,000 patients. Experiences and expectations of rare disease patients on diagnosis and care in Europe, A report based on the EurordisCare2 and EurordisCare3 Survey. Available from: http://www.eurordis.org/IMG/ pdf/voice_12000_patients/EURORDISCARE_FULLBOOKr.pdf
  • 19. Devaney R, Pasalodos S, Suri M, Bush A, Bhatt JM. Ataxia telangiectasia: presentation and diagnostic delay. Arch Dis Child 2017;102:328-330.
  • 20. Chiò A. ISIS Survey: an international study on the diagnostic process and its implications in amyotrophic lateral sclerosis. J Neurol 1999;246(Suppl 3):III1-5.
  • 21. Ruiz-Lopez M, Freitas ME, Oliveira LM, et al. Diagnostic delay in Parkinson's disease caused by PRKN mutations. Parkinsonism Relat Disord 2019;63:217-220.
  • 22. Tadic V, Kasten M, Brüggemann N, et al. Dopa-responsive dystonia revisited: diagnostic delay, residual signs, and nonmotor signs. Arch Neurol 2012;69:1558-1562.
  • 23. van Geel BM, Assies J, Haverkort EB, et al. Delay in diagnosis of X-linked adrenoleukodystrophy. Clin Neurol Neurosurg 1993;95:115-120.
APA Yetkin M, GULTEKIN M, Akcakoyunlu M, Baydemir R, Sarilar A, Canpolat M, Per H (2022). Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. , 97 - 101. 10.4274/tnd.2022.26780
Chicago Yetkin Mehmet Fatih,GULTEKIN MURAT,Akcakoyunlu Merve,Baydemir Recep,Sarilar Ayse Çağlar,Canpolat Mehmet,Per Hüseyin Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. (2022): 97 - 101. 10.4274/tnd.2022.26780
MLA Yetkin Mehmet Fatih,GULTEKIN MURAT,Akcakoyunlu Merve,Baydemir Recep,Sarilar Ayse Çağlar,Canpolat Mehmet,Per Hüseyin Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. , 2022, ss.97 - 101. 10.4274/tnd.2022.26780
AMA Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. . 2022; 97 - 101. 10.4274/tnd.2022.26780
Vancouver Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. . 2022; 97 - 101. 10.4274/tnd.2022.26780
IEEE Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H "Diagnostic Delay and Clinical Features in Friedreich’s Ataxia." , ss.97 - 101, 2022. 10.4274/tnd.2022.26780
ISNAD Yetkin, Mehmet Fatih vd. "Diagnostic Delay and Clinical Features in Friedreich’s Ataxia". (2022), 97-101. https://doi.org/10.4274/tnd.2022.26780
APA Yetkin M, GULTEKIN M, Akcakoyunlu M, Baydemir R, Sarilar A, Canpolat M, Per H (2022). Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. Türk Nöroloji Dergisi, 28(2), 97 - 101. 10.4274/tnd.2022.26780
Chicago Yetkin Mehmet Fatih,GULTEKIN MURAT,Akcakoyunlu Merve,Baydemir Recep,Sarilar Ayse Çağlar,Canpolat Mehmet,Per Hüseyin Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. Türk Nöroloji Dergisi 28, no.2 (2022): 97 - 101. 10.4274/tnd.2022.26780
MLA Yetkin Mehmet Fatih,GULTEKIN MURAT,Akcakoyunlu Merve,Baydemir Recep,Sarilar Ayse Çağlar,Canpolat Mehmet,Per Hüseyin Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. Türk Nöroloji Dergisi, vol.28, no.2, 2022, ss.97 - 101. 10.4274/tnd.2022.26780
AMA Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. Türk Nöroloji Dergisi. 2022; 28(2): 97 - 101. 10.4274/tnd.2022.26780
Vancouver Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H Diagnostic Delay and Clinical Features in Friedreich’s Ataxia. Türk Nöroloji Dergisi. 2022; 28(2): 97 - 101. 10.4274/tnd.2022.26780
IEEE Yetkin M,GULTEKIN M,Akcakoyunlu M,Baydemir R,Sarilar A,Canpolat M,Per H "Diagnostic Delay and Clinical Features in Friedreich’s Ataxia." Türk Nöroloji Dergisi, 28, ss.97 - 101, 2022. 10.4274/tnd.2022.26780
ISNAD Yetkin, Mehmet Fatih vd. "Diagnostic Delay and Clinical Features in Friedreich’s Ataxia". Türk Nöroloji Dergisi 28/2 (2022), 97-101. https://doi.org/10.4274/tnd.2022.26780