부산대학교 도서관

INTRODUCTION Inflammatory myopathies (IMs) with an autoimmune etiology are rarely seen in childhood (1,2). Juvenile dermatomyositis, juvenile polymyositis and overlap myositis are the most frequent types of IMs. IMs are [...]
Inflammatory myopathies are autoimmune disorders rarely seen in childhood. Normally high-dose corticosteroid is the current treatment for inflammatory myopathies. For a specific subgroup of patients with inflammatory myopathy with cytochrome oxidase (COX)-negative myofibers that do not typically respond to corticosteroid treatment, and methotrexate (MTX) is used for therapy. Herein we present a 10-year-old girl who initially received clinical diagnosis of juvenile inflammatory myopathy which did not respond to corticosteroid treatment. Examination of her muscle biopsy specimen showed the presence of COX-negative muscle fibers which are very rarely seen in childhood inflammatory myopathies, and she was diagnosed as inflammatory myopathy characterized with COX-negative myofibers. The patient, who recovered with MTX therapy underwent genetic examination 3 years after the treatment was terminated. The sequence analyses of mitochondrial DNA (mtDNA) identified 19 variants in the rRNA, ND2, ND4, ND5, COXi, COX3, and CytB genes of the mtDNA of the patient and her mother. These mutations generally induce the production of synonym amino acids. However, four missense mutations on the ND4, ATP6, and CytB genes have caused structural changes in amino acids. None of these mutations have been previously reported as pathogenic variants. We have thought that these variations in such essential genes might destabilize mtDNA and could probably affect the ATP synthesis in our patient. Our final diagnosis was established based on abnormal inflammatory response induced by a hereditary mtDNA defect in a child with mitochondrial myopathy, rather than an inflammatory myopathy with COX deficiency. Keywords: Childhood inflammatory myopathy, polymyositis with COX-negative myofibers, ATP6 synthase gene, ND4 gene, CytB gene, mitochondrial myopathy Enflamatuvar miyopatiler, cocukluk caginda nadiren gorulen otoimmun bozukluklardir. Normalde yuksek doz kortikosteroid, enflamatuvar miyopatiler icin guncel tedavidir. Sitokrom oksidaz (COX) negatif miyofiberleri olan enflamatuvar miyopatili bir hasta alt grubu tipik olarak kortikosteroid tedavisine yanit vermez. Bu durumda tedavi icin metotreksat kullanilir. Burada baflangicta klinik olarak juvenil enflamatuvar miyopati tanisi konulan ve kortikosteroid tedavisine yanit vermeyen 10 yafinda bir kiz cocugu sunulmaktadir. Kas biyopsisinde cocukluk cagi enflamatuvar miyopatilerinde cok nadir gorulen COX-negatif kas lifleri goruldu ve COX-negatif miyofiberli enflamatuvar miyopati tanisi aldi. Metotreksat tedavisi ile iyilefen hastada, tedavi kesildikten 3 yil sonra genetic inceleme yapilabildi. Mitokondriyal DNA dizi analizlerinde hastanin ve annesinin mitokondrial DNA'sinin rRNA, ND2, ND4, ND5, COXi, COX3 ve CytB genlerinde 19 varyant tespit edildi. Bu mutasyonlar genellikle ayni amino asitlerin uretimine neden olmaktaydi. Ancak ND4, ATP6 ve CytB genlerindeki dort missens mutasyon, amino asitlerin degifmesine neden olmuftu. Bu mutasyonlarin hicbiri daha once patojenik varyantlar olarak bildirilmemifti. Bu temel genlerdeki varyasyonlarin, mitokondrial DNA'nin kararsizligina neden olabilecegini ve sunulan hastada ATP sentezini etkileyebilecegini dufunduk. Genetik inceleme sonrasi hastayi COX enzim defekti olan enflamatuvar bir miyopatiden cok, kalitsal mitokondrial DNA kusurunun neden oldugu anormal enflamatuvar yanit gozlenen mitokondrial miyopati olarak degerlendirdik. Anahtar kelimeler: Cocukluk cagi enflamatuvar miyopatisi, COX-negatif miyofiberli polimiyozit, ATP6 sentez geni, ND4 geni, CytB geni, mitokondriyal miyopati