Bindu Parayil Sankaran, Govindaraju Chikanna, Sonam Kothari, Nagappa Madhu, Chiplunkar Shwetha, Kumar Rakesh, Gayathri Narayanappa, Bharath M M Srinivas, Arvinda Hanumanthapura R, Sinha Sanjib, Khan Nahid Akthar, Govindaraj Periyasamy, Nunia Vandana, Paramasivam Arumugam, Thangaraj Kumarasamy, Taly Arun B
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Mitochondrion. 2016 Mar;27:1-5. doi: 10.1016/j.mito.2015.12.009. Epub 2016 Jan 4.
There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders.
The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006-2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively.
The study cohort included 18 patients (age range: 18 months-50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n=11), SURF1 mutations (n=4) and POLG1(n=3). Axonal neuropathy was noted in 12 patients (sensori-motor:n=4; sensory:n=4; motor:n=4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy.
A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder.
针对具有基因特征的线粒体疾病患者大样本队列中的周围神经病变进行研究的相对较少。本研究旨在分析一组线粒体疾病患者的周围神经病变模式。
研究对象来自于8年期间(2006 - 2013年)确诊的52例基因诊断为线粒体疾病的患者队列。所有患者均接受了神经传导研究,那些提示有周围神经病变异常的患者被纳入研究。对他们的表型特征、基因型、周围神经病变模式和神经传导异常进行回顾性分析。
研究队列包括18例患者(年龄范围:18个月至50岁,男:女 = 1.2:1)。基因型包括线粒体DNA点突变(n = 11)、SURF1突变(n = 4)和POLG1(n = 3)。12例患者出现轴索性神经病变(感觉运动型:n = 4;感觉型:n = 4;运动型:n = 4),6例出现脱髓鞘性神经病变。表型 - 基因型相关性显示,mtDNA点突变中主要为轴索性神经病变,SURF1中为脱髓鞘性神经病变。POLG相关疾病患者既有感觉性共济失调性神经病变又有轴索性神经病变。
仔细分析家族史、临床表现、生化、组织化学和结构分析可能有助于揭示周围神经病变患者的线粒体病因,并可能有助于进行靶向基因检测。 Leigh综合征中出现脱髓鞘性神经病变可能提示潜在的SURF1突变。伴有其他线粒体特征的感觉性共济失调性神经病变应增加POLG相关疾病的可能性。