Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene.
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.
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.
Madhu
M
Nagappa
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. Electronic address: drpsbindu@yahoo.co.in.
Parayil Sankaran
PS
Bindu
Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India; Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Shwetha
S
Chiplunkar
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.
Periasamy
P
Govindaraj
Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India; Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Gayathri
G
Narayanappa
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Ayyappan
A
Krishnan
Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
M M Srinivas
MM
Bharath
Department of Neuro-Imaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Aarthi
A
Swaminathan
Department of Neuro-Imaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Jitender
J
Saini
Department of Neuro-Imaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Hanumanthapura R
HR
Arvinda
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Sanjib
S
Sinha
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India.
Pavagada S
PS
Mathuranath
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.
Arun B
AB
Taly
D000612:4-Aminobutyrate Transaminase / Q000172:deficiency / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D002658:Developmental Disabilities / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D003937:Diagnosis, Differential; D006970:Disorders of Excessive Somnolence / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D006948:Hyperkinesis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D007223:Infant; D020125:Mutation, Missense; D017386:Sequence Homology, Amino Acid
D000612:4-Aminobutyrate Transaminase
ABAT; GABA; Hyperkinetic movement disorder; Hypersomnolence