Phenotype of GABA-transaminase Deficiency

Overview

Journal Neurology

Specialty Neurology

Date 2017 Apr 16

PMID 28411234

Citations 26

Authors

Mary Kay Koenig

Ryan Hodgeman

James J Riviello

Wendy Chung

Jennifer Bain

Claudia A Chiriboga

Kazushi Ichikawa

Hitoshi Osaka

Megumi Tsuji

K Michael Gibson

Penelope E Bonnen

Phillip L Pearl

Affiliations

Soon will be listed here.

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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