Öz
Mitokondriyal hastalıklar, oksidatif fosforilasyondaki bozukluk nedeniyle hücresel enerji metabolizmasının bozulmasıyla karakterize edilen heterojen bir kalıtsal metabolik hastalık grubudur. Bu hastalıklar genellikle sinir sistemi, kaslar, kalp ve karaciğer gibi birçok organı etkileyen geniş bir klinik spektrum sergileyerek tanıyı zorlaştırmaktadır. Bu retrospektif çalışma, Ankara Etlik Şehir Hastanesi Çocuk Metabolizma Kliniği’nde mitokondriyal hastalık tanısı alan 19 pediatrik hastanın klinik, laboratuvar ve genetik özelliklerini değerlendirmektedir. En sık görülen klinik bulgular arasında hipotoni, epilepsi ve nöromotor gelişim geriliği yer alırken, biyokimyasal analizlerde sıklıkla laktik asidoz ve anormal metabolik profiller saptanmıştır. Genetik analizler, çeşitli mitokondriyal DNA ve nükleer DNA mutasyonlarını belirleyerek kapsamlı moleküler tanıların önemini vurgulamaktadır.
Anahtar Kelimeler
Kalıtsal metabolizma hastalıkları mitokondriyal hastalıklar NGS
Kaynakça
- Rahman S. Mitochondrial diseases and status epilepticus. Epilepsia. 2018;59:70-7.
- Schirrmacher V. Mitochria at work: new insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines. 2020;8(11):526.
- Bergman O, Ben-Shachar D. Mitochondrial oxidative phosphorylation system (OXPHOS) deficits in schizophrenia: possible interactions with cellular processes. Can J Psychiatry. 2016;61(8):457-69.
- Zhu Z, Wang X. Significance of mitochondria DNA mutations in diseases. In: Mitochondrial DNA and diseases. 2017. p. 219-30.
- Gusic M, Prokisch H. Genetic basis of mitochondrial diseases. FEBS Lett. 2021;595(8):1132-58.
- Schon KR, Ratnaike T, van den Ameele J, Horvath R, Chinnery PF. Mitochondrial diseases: a diagnostic revolution. Trends Genet. 2020;36(9):702-17.
- Schlieben LD, Prokisch H. The dimensions of primary mitochondrial disorders. Front Cell Dev Biol. 2020;8:600079.
- Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, et al. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015;17(9):689-701.
- Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2(1):16080.
- Barrientos A, Fontanesi F, Díaz F. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays. Curr Protoc Hum Genet. 2009;63(1):19.3.1-19.3.4.
- Stenton SL, Prokisch H. Genetics of mitochondrial diseases: Identifying mutations to help diagnosis. EBioMedicine. 2020;56.
- Watson E, Davis R, Sue CM. New diagnostic pathways for mitochondrial disease. J Transl Genet Genom. 2020;4(3):188-202.
- Ng YS, Bindoff LA, Gorman GS, Klopstock T, Kornblum C, Mancuso M, et al. Mitochondrial disease in adults: recent advances and future promise. Lancet Neurol. 2021;20(7):573-84.
- Rambani V, Hromnikova D, Gasperikova D, Skopkova M. Mitochondria and mitochondrial disorders: An overview update. Endocr Regul. 2022;56(3):232-48.
- Di Donato S. Multisystem manifestations of mitochondrial disorders. J Neurol. 2009;256:693-710.
- Grigalionienė K, Burnytė B, Ambrozaitytė L, Utkus A. Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease. Orphanet J Rare Dis. 2023;18(1):307.
- Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X, et al. Mitochondrial diseases: from molecular mechanisms to therapeutic advances. Signal Transduct Target Ther. 2025;10(1):9.
- Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2(1):1-22.
- Moggio M, Colombo I, Peverelli L, Villa L, Xhani R, Testolin S, et al. Mitochondrial disease heterogeneity: a prognostic challenge. Acta Myol. 2014;33(2):86.
- Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R, et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol. 2009;11(6):414-30.
- Gruosso F, Montano V, Simoncini C, Siciliano G, Mancuso M. Therapeutical management and drug safety in mitochondrial diseases—update 2020. J Clin Med. 2020;10(1):94.
Öz
Background: Mitochondrial diseases are a heterogeneous group of inherited metabolic disorders characterized by dysfunction in oxidative phosphorylation, leading to impaired cellular energy metabolism. These disorders present with a broad clinical spectrum, often involving the nervous system, muscles, heart, and liver, making diagnosis complex.
Methods: This retrospective study evaluates the clinical, laboratory, and genetic characteristics of 19 pediatric patients diagnosed with mitochondrial diseases at the pediatric metabolism clinic.
Results: The most common clinical findings were hypotonia (52.6%), lactic acidosis (26.3%), and seizures (21.1%), followed by neuromotor delay (10.5%) and bilateral optic atrophy (10.5%). These findings reflect the multisystemic involvement and neurological predominance typical of mitochondrial disorders. Biochemical analyses frequently revealed abnormal metabolic profiles supportive of mitochondrial dysfunction.
Conclusions: Genetic analyses identified various mitochondrial DNA and nuclear DNA mutations, underscoring the importance of comprehensive molecular diagnostics. Molecular testing improved diagnostic accuracy and facilitated more tailored patient management, including early initiation of supportive treatments and genetic counselling.
Anahtar Kelimeler
Kaynakça
- Rahman S. Mitochondrial diseases and status epilepticus. Epilepsia. 2018;59:70-7.
- Schirrmacher V. Mitochria at work: new insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines. 2020;8(11):526.
- Bergman O, Ben-Shachar D. Mitochondrial oxidative phosphorylation system (OXPHOS) deficits in schizophrenia: possible interactions with cellular processes. Can J Psychiatry. 2016;61(8):457-69.
- Zhu Z, Wang X. Significance of mitochondria DNA mutations in diseases. In: Mitochondrial DNA and diseases. 2017. p. 219-30.
- Gusic M, Prokisch H. Genetic basis of mitochondrial diseases. FEBS Lett. 2021;595(8):1132-58.
- Schon KR, Ratnaike T, van den Ameele J, Horvath R, Chinnery PF. Mitochondrial diseases: a diagnostic revolution. Trends Genet. 2020;36(9):702-17.
- Schlieben LD, Prokisch H. The dimensions of primary mitochondrial disorders. Front Cell Dev Biol. 2020;8:600079.
- Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, et al. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015;17(9):689-701.
- Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2(1):16080.
- Barrientos A, Fontanesi F, Díaz F. Evaluation of the mitochondrial respiratory chain and oxidative phosphorylation system using polarography and spectrophotometric enzyme assays. Curr Protoc Hum Genet. 2009;63(1):19.3.1-19.3.4.
- Stenton SL, Prokisch H. Genetics of mitochondrial diseases: Identifying mutations to help diagnosis. EBioMedicine. 2020;56.
- Watson E, Davis R, Sue CM. New diagnostic pathways for mitochondrial disease. J Transl Genet Genom. 2020;4(3):188-202.
- Ng YS, Bindoff LA, Gorman GS, Klopstock T, Kornblum C, Mancuso M, et al. Mitochondrial disease in adults: recent advances and future promise. Lancet Neurol. 2021;20(7):573-84.
- Rambani V, Hromnikova D, Gasperikova D, Skopkova M. Mitochondria and mitochondrial disorders: An overview update. Endocr Regul. 2022;56(3):232-48.
- Di Donato S. Multisystem manifestations of mitochondrial disorders. J Neurol. 2009;256:693-710.
- Grigalionienė K, Burnytė B, Ambrozaitytė L, Utkus A. Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease. Orphanet J Rare Dis. 2023;18(1):307.
- Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X, et al. Mitochondrial diseases: from molecular mechanisms to therapeutic advances. Signal Transduct Target Ther. 2025;10(1):9.
- Gorman GS, Chinnery PF, DiMauro S, Hirano M, Koga Y, McFarland R, et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016;2(1):1-22.
- Moggio M, Colombo I, Peverelli L, Villa L, Xhani R, Testolin S, et al. Mitochondrial disease heterogeneity: a prognostic challenge. Acta Myol. 2014;33(2):86.
- Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R, et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol. 2009;11(6):414-30.
- Gruosso F, Montano V, Simoncini C, Siciliano G, Mancuso M. Therapeutical management and drug safety in mitochondrial diseases—update 2020. J Clin Med. 2020;10(1):94.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Metabolik Tıp |
| Bölüm | ORIGINAL ARTICLE |
| Yazarlar | |
| Yayımlanma Tarihi | 28 Eylül 2025 |
| Gönderilme Tarihi | 25 Şubat 2025 |
| Kabul Tarihi | 15 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 6 Sayı: 3 |
Archives of Current Medical Research (ACMR), araştırmaları ücretsiz sunmanın daha büyük bir küresel bilgi alışverişini desteklediğini göz önünde bulundurarak, tüm içeriğe anında açık erişim sağlar. Kamunun erişimine açık olması, daha büyük bir küresel bilgi alışverişini destekler.
http://www.acmronline.org/