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

Phenotype of GABA-transaminase deficiency

Mary Kay Koenig  1 , Ryan Hodgeman  1 , James J Riviello  1 , Wendy Chung  1 , Jennifer Bain  1 , Claudia A Chiriboga  1 , Kazushi Ichikawa  1 , Hitoshi Osaka  1 , Megumi Tsuji  1 , K Michael Gibson  1 , Penelope E Bonnen  1 , Phillip L Pearl  2
Affiliations
Review

Phenotype of GABA-transaminase deficiency

Mary Kay Koenig et al. Neurology. .

Abstract

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.

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Figures

Figure 1
Figure 1. MRI in γ-aminobutyric acid transaminase deficiency
Axial MRI, fluid-attenuated inversion recovery sequence (patient 1, age 4 years), with prominent enlargement of sylvian fissures and pontomesencephalic cisterns.
Figure 2
Figure 2. Pre and post-flumazenil EEG
EEG of patient 2 at (A) 21 months of age, with high-voltage polymorphic delta and multifocal and generalized spike-wave; and (B) 26 months, with improved background organization but some persistence of generalized epileptiform activity (settings in all figures: HFF 70 Hz, LFF 1 Hz, sensitivity 10 μV/mm).
See this image and copyright information in PMC

References

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Supplementary concepts