Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene

详细信息    查看全文

• 作者：Madhu Nagappa^a ; ^b ; Parayil Sankaran Bindu^a ; ^b ; ^{drpsbindu@yahoo.co.in} ; Shwetha Chiplunkar^b ; ^c ; Periasamy Govindaraj^a ; ^b ; Gayathri Narayanappa^b ; ^d ; Ayyappan Krishnan^a ; M.M. Srinivas Bharath^e ; Aarthi Swaminathan^f ; Jitender Saini^f ; Hanumanthapura R. Arvinda^f ; Sanjib Sinha^a ; Pavagada S. Mathuranath^a ; Arun B. Taly^a ; ^b
• 关键词：ABAT ; GABA ; Hyperkinetic movement disorder ; Hypersomnolence
• 刊名：Brain and Development
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：39
• 期：2
• 页码：161-165
• 全文大小：962 K
• 卷排序：39

文摘

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 18 months, 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 2.2 ppm and 2.4 ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18 months. 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.