Hemelsoet Dimitri M, Vanlander Arnaud V, Smet Joél, Vantroys Elise, Acou Marjan, Goethals Ingeborg, Sante Tom, Seneca Sara, Menten Bjorn, Van Coster Rudy
Department of Neurology (D.M.H.), Ghent University Hospital; Department of Pediatrics (A.V.V., J.S., E.V., R.V.C.), Division of Pediatric Neurology and Metabolism, Ghent University Hospital; Department of Radiology (M.A.), Ghent University Hospital; Department of Nuclear Medicine (I.G.), Ghent University Hospital; Center for Medical Genetics Ghent (T.S., B.M.), Ghent University, Belgium; and Center for Medical Genetics (S.S.), UZ Brussel and Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium.
Neurol Genet. 2018 Nov 27;4(6):e298. doi: 10.1212/NXG.0000000000000298. eCollection 2018 Dec.
To report the clinical, radiologic, biochemical, and molecular characteristics in a 46-year-old participant with adult-onset Leigh syndrome (LS), followed by parkinsonism.
Case description with diagnostic workup included blood and CSF analysis, skeletal muscle investigations, blue native polyacrylamide gel electrophoresis, whole exome sequencing targeting nuclear genes involved in mitochondrial transcription and translation, cerebral MRI, 123I-FP-CIT brain single-photon emission computed tomography (SPECT), and C-11 raclopride positron emission tomography (PET).
The participant was found to have a defect in the oxidative phosphorylation caused by a c.626C>T mutation in the gene coding for mitochondrial methionyl-tRNA formyltransferase (), which is a pathogenic mutation affecting intramitochondrial protein translation. The proband had a normal concentration of lactate in blood and no abnormal microscopic findings in skeletal muscle. Cerebral MRI showed bilateral lesions in the striatum, mesencephalon, pons, and medial thalamus. Lactate concentration in CSF was increased. FP-CIT SPECT and C-11 raclopride PET demonstrated a defect in the dopaminergic system.
We report on a case with adult-onset LS related to a mutation. Two years after the onset of symptoms of LS, the proband developed a parkinson-like disease. The c.626C>T mutation is the most common pathogenic mutation found in 22 patients reported earlier in the literature with a defect in . The age of the previously reported cases varied between 14 months and 24 years. Our report expands the phenotypical spectrum of -related neurologic disease and provides clinical evidence for involvement of in extrapyramidal syndromes.
报告一名46岁成年起病的 Leigh 综合征（LS）患者的临床、放射学、生化和分子特征，该患者随后出现帕金森综合征。
病例描述及诊断检查包括血液和脑脊液分析、骨骼肌检查、蓝色原代聚丙烯酰胺凝胶电泳、针对参与线粒体转录和翻译的核基因的全外显子测序、脑部磁共振成像（MRI）、123I - FP - CIT 脑单光子发射计算机断层扫描（SPECT）以及 C - 11 雷氯必利正电子发射断层扫描（PET）。
该患者被发现由于线粒体甲硫氨酰 - tRNA 甲酰基转移酶基因（）中的 c.626C>T 突变导致氧化磷酸化缺陷，这是一种影响线粒体内蛋白质翻译的致病突变。先证者血液中乳酸浓度正常，骨骼肌无异常微观发现。脑部 MRI 显示纹状体、中脑、脑桥和内侧丘脑双侧病变。脑脊液中乳酸浓度升高。FP - CIT SPECT 和 C - 11 雷氯必利 PET 显示多巴胺能系统存在缺陷。
我们报告了一例与 突变相关的成年起病的 LS 病例。在 LS 症状出现两年后，先证者发展为帕金森样疾病。c.626C>T 突变是文献中先前报道的22例 缺陷患者中最常见的致病突变。先前报道病例的年龄在14个月至24岁之间。我们的报告扩展了与 相关的神经疾病的表型谱，并为 参与锥体外系综合征提供了临床证据。
