Nagappa Madhu, Bindu Parayil Sankaran, Chiplunkar Shwetha, Govindaraj Periasamy, Narayanappa Gayathri, Krishnan Ayyappan, Bharath M M Srinivas, Swaminathan Aarthi, Saini Jitender, Arvinda Hanumanthapura R, Sinha Sanjib, Mathuranath Pavagada S, Taly Arun B
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Brain Dev. 2017 Feb;39(2):161-165. doi: 10.1016/j.braindev.2016.08.005. Epub 2016 Sep 3.
Deficiency of gamma-amino-butyrate aminotransferase (ABAT) is a rare inherited disorder. A six-month-old girl presented with hyper-somnolence, hyperkinetic movements of distal extremities during wakefulness, hypotonia, bi-pyramidal signs, and impaired response to sound and visual stimuli. Brain MRI at five months showed restricted diffusion along the internal capsule and genu of corpus callosum. A follow up MRI at 18months, showed hyperintensities in brainstem, external and internal capsule, 'trilaminated' appearance of posterior limb of internal capsule and dysmyelination of sub-cortical white matter. MRS showed a peak between 2.2ppm and 2.4ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18months. Targeted exome sequencing revealed compound heterozygous missense variations in ABAT resulting in its reduced function. We report the novel association of hypersomnolence and hyperkinetic movement disorder with ABAT variations thus expanding the clinical spectrum of this uncommon neuro-metabolic disorder and discuss the emerging role of GABA in pathways regulating sleep-wake cycle and movement disorders.
γ-氨基丁酸转氨酶（ABAT）缺乏症是一种罕见的遗传性疾病。一名6个月大的女孩出现嗜睡、清醒时远端肢体运动亢进、肌张力低下、双侧锥体束征以及对声音和视觉刺激反应受损。5个月时的脑部MRI显示沿内囊和胼胝体膝部扩散受限。18个月时的随访MRI显示脑干、外囊和内囊出现高信号，内囊后肢呈“三层”外观以及皮质下白质脱髓鞘。磁共振波谱显示在2.2ppm至2.4ppm之间有一个峰，对应谷氨酰胺、谷氨酸和GABA。脑电图在6个月时正常，但在18个月时显示多灶性癫痫样放电。靶向外显子组测序揭示ABAT存在复合杂合错义变异，导致其功能降低。我们报告了嗜睡和运动亢进性运动障碍与ABAT变异的新关联，从而扩大了这种罕见神经代谢疾病的临床谱，并讨论了GABA在调节睡眠-觉醒周期和运动障碍途径中的新作用。
