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

• Published in: Brain & development (Tokyo. 1979) 2017-02, Vol.39 (2), p.161-165
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 4-Aminobutyrate Transaminase - deficiency; 4-Aminobutyrate Transaminase - genetics; ABAT; Brain - diagnostic imaging; Brain - physiopathology; Developmental Disabilities - diagnostic imaging; Developmental Disabilities - genetics; Developmental Disabilities - physiopathology; Diagnosis, Differential; Disorders of Excessive Somnolence - diagnostic imaging; Disorders of Excessive Somnolence - genetics; Disorders of Excessive Somnolence - physiopathology; Female; Follow-Up Studies; GABA; Heterozygote; Humans; Hyperkinesis - diagnostic imaging; Hyperkinesis - genetics; Hyperkinesis - physiopathology; Hyperkinetic movement disorder; Hypersomnolence; Infant; Mutation, Missense; Neurology; Sequence Homology, Amino Acid
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2016.08.005

Abstract 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.