Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients

• DOI: 10.1007/s10545-017-0042-6
• Publication Date: 2017-04-20T13:30:15Z
• Authors: Erika Ogawa; Masaru Shimura; Takuya Fushimi; Makiko Tajika; Keiko Ichimoto; Ayako Matsunaga; Tomoko Tsuruoka; Mika Ishige; Tatsuo Fuchigami; Taro Yamazaki; Masato Mori; Masakazu Kohda; Yoshihito Kishita; Yasushi Okazaki; Shori Takahashi; Akira Ohtake; Kei Murayama
• Keywords: Human genetics

Abstract Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It clinically diagnosed by typical manifestations characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS essential for deeper understanding the disease, which may lead to development new therapies cure. The aim this study was evaluate clinical validity various diagnostic tools in confirming MRC Leigh‐like (LL). results enzyme assays, molecular analysis, cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 biochemically genetically verified, 34 had reduced activity but no causative mutations. Seven patients with normal complex activities mutations MT‐ATP6 gene. Five further identified Conversely, 12 out 60 assays performed verified returned results. No biochemical genetic background confirmed 19 patients. OCR ten negative assay Inconsistent between fibroblast skeletal muscle biopsy samples observed 33% 37 simultaneously analyzed cases. These data suggest that highest reached using combined enzymatic approach, analyzing more than one type biological materials where suitable. Microscale oxygraphy detected impairment 50% cases defect activities.