Phenotype of GABA-transaminase Deficiency

Neurology. 2017 May 16;88(20):1919-1924. doi: 10.1212/WNL.0000000000003936. Epub 2017 Apr 14.


Objective: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype.

Methods: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil.

Results: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. EEGs showed burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Five of the 10 patients are currently alive with age at last follow-up between 18 months and 9.5 years. Treatment with continuous flumazenil was implemented in 2 patients. One patient, with a milder phenotype, began treatment at age 21 months and has continued for 20 months with improved alertness and less excessive adventitious movements. The second patient had a more severe phenotype and was 7 years of age at initiation of flumazenil, which was not continued.

Conclusions: GABA-transaminase deficiency presents with neonatal or infantile-onset encephalopathy including hypersomnolence and choreoathetosis. A widened phenotypic spectrum is reported as opposed to lethality by 2 years of age. The GABA-A benzodiazepine receptor antagonist flumazenil may represent a therapeutic strategy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • 4-Aminobutyrate Transaminase / deficiency*
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / drug therapy
  • Amino Acid Metabolism, Inborn Errors / mortality
  • Amino Acid Metabolism, Inborn Errors / physiopathology*
  • Brain / diagnostic imaging
  • Brain / physiopathology
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Female
  • Flumazenil / therapeutic use
  • Follow-Up Studies
  • GABA Modulators / therapeutic use
  • Humans
  • Infant
  • Male
  • Phenotype


  • GABA Modulators
  • Flumazenil
  • 4-Aminobutyrate Transaminase

Supplementary concepts

  • Gamma aminobutyric acid transaminase deficiency