Gamma-Aminobutyric Acid Transaminase (GABA-T) Deficiency in a Consanguineous Saudi Family: A Case Report and Literature Review

Abstract

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is a rare, autosomal recessive disorder caused by mutations in the 4-aminobutyrate aminotransferase (ABAT) gene, which encodes an enzyme involved in GABA catabolism. It is characterized by severe psychomotor retardation, early-onset epileptic encephalopathy, intractable seizures, hypotonia, hyperreflexia, movement disorder, hypersomnolence, and early childhood mortality. It is associated with elevated free GABA in cerebrospinal fluid (CSF), GABA-T deficiency in cultured lymphoblasts, hypomyelination on brain magnetic resonance imaging (MRI), and elevated GABA level in the basal ganglia on proton magnetic resonance spectroscopy (MRS). Only 14 cases have been published in the literature. A rare case of infantile epileptic encephalopathy caused by GABA-T deficiency resulting from a previously unreported homozygous missense mutation in the ABAT gene is described. Our findings add to the phenotypic, neuroradiological, and genetic spectrum of ABAT mutations.

Keywords

GABA-T deficiency - 4-aminobutyrate aminotransferase - ABAT gene - MRI

Ethical Approval

Written informed consent for the publication of this case report was obtained from the parents of the patient. The author declares that ethical approval was not required for this case report.

Publication History

Received: 30 January 2022

Accepted: 29 August 2022

Article published online:
28 October 2022

• References

• 1 Gibson KM, Sweetman L, Nyhan WL, Jansen I. Demonstration of 4-aminobutyric acid aminotransferase deficiency in lymphocytes and lymphoblasts. J Inherit Metab Dis 1985; 8 (04) 204-208
• 2 Jakobs C, Jaeken J, Gibson KM. Inherited disorders of GABA metabolism. J Inherit Metab Dis 1993; 16 (04) 704-715
• 3 Jaeken J, Casaer P, de Cock P. et al. Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics 1984; 15 (03) 165-169
• 4 Koenig MK, Hodgeman R, Riviello JJ. et al. Phenotype of GABA-transaminase deficiency. Neurology 2017; 88 (20) 1919-1924
• 5 Pan JW, Williamson A, Cavus I. et al. Neurometabolism in human epilepsy. Epilepsia 2008; 49 (Suppl. 03) 31-41
• 6 Nutzenadel W. Disorders of beta-alanine, 4-aminobutyrate (GABA), carnosine, and homocarnosine. In: Fernandes J, Saudubray J-M, Tada K. eds. Inborn Metabolic Diseases: Diagnosis and treatment. New York: Springer-Verlag; 1990: 337-343
• 7 Pearl PL, Parviz M, Vogel K, Schreiber J, Theodore WH, Gibson KM. Inherited disorders of gamma-aminobutyric acid metabolism and advances in ALDH5A1 mutation identification. Dev Med Child Neurol 2015; 57 (07) 611-617
• 8 Ichikawa K, Tsuji M, Tsuyusaki Y, Tomiyasu M, Aida N, Goto T. Serial magnetic resonance imaging and ¹ H-magnetic resonance spectroscopy in GABA transaminase deficiency: a case report. JIMD Rep 2019; 43: 7-12
• 9 Parviz M, Vogel K, Gibson KM, Pearl PL. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 2014; 3 (04) 217-227
• 10 Medina-Kauwe LK, Tobin AJ, De Meirleir L. et al. 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis 1999; 22 (04) 414-427
• 11 Anazi S, Maddirevula S, Faqeih E. et al. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry 2017; 22 (04) 615-624
• 12 Oshi A, Alfaifi A, Seidahmed MZ. et al. GABA transaminase deficiency. Case report and literature review. Clin Case Rep 2021; 9 (03) 1295-1298
• 13 Hegde AU, Karnavat PK, Vyas R, DiBacco ML, Grant PE, Pearl PL. GABA transaminase deficiency with survival into adulthood. J Child Neurol 2019; 34 (04) 216-220
• 14 Nagappa M, Bindu PS, Chiplunkar S. et al. Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene. Brain Dev 2017; 39 (02) 161-165
• 15 Louro P, Ramos L, Robalo C. et al. Phenotyping GABA transaminase deficiency: a case description and literature review. J Inherit Metab Dis 2016; 39 (05) 743-747
• 16 Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE. Personalized medicine approach confirms a milder case of ABAT deficiency. Mol Brain 2016; 9 (01) 93
• 17 Besse A, Wu P, Bruni F. et al. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. Cell Metab 2015; 21 (03) 417-427
• 18 Tsuji M, Aida N, Obata T. et al. A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. J Inherit Metab Dis 2010; 33 (01) 85-90