Phenotype of GABA-transaminase deficiency

作者：Koenig Mary Kay; Hodgeman Ryan; Riviello James J; Chung Wendy; Bain Jennifer; Chiriboga Claudia A; Ichikawa Kazushi; Osaka Hitoshi; Tsuji Megumi; Gibson K Michael; Bonnen Penelope E; Pearl Phillip L

来源：Neurology, 2017, 88(20): 1919-1924.

DOI：10.1212/WNL.0000000000003936

Objective: We report a case series of 10 patients with gamma-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.

• 出版日期2017-5-16