Mary Kay Koenig1, Ryan Hodgeman1, James J Riviello1, Wendy Chung1, Jennifer Bain1, Claudia A Chiriboga1, Kazushi Ichikawa1, Hitoshi Osaka1, Megumi Tsuji1, K Michael Gibson1, Penelope E Bonnen1, Phillip L Pearl2. 1. From Child and Adolescent Neurology (M.K.K.), University of Texas Medical School, Houston; Neurology (R.H., P.L.P.), Boston Children's Hospital, Harvard Medical School, MA; Child Neurology (J.J.R., W.C., J.B., C.A.C.), Columbia University School of Medicine, New York, NY; Neurology (K.I., M.T.), Kanagawa Children's Medical Center, Yokohama; Pediatrics (H.O.), Jichi Medical School, Tochigi, Japan; Experimental and Systems Pharmacology (K.M.G.), Washington State University, Spokane; and Molecular and Human Genetics (P.E.B.), Baylor College of Medicine, Houston, TX. 2. From Child and Adolescent Neurology (M.K.K.), University of Texas Medical School, Houston; Neurology (R.H., P.L.P.), Boston Children's Hospital, Harvard Medical School, MA; Child Neurology (J.J.R., W.C., J.B., C.A.C.), Columbia University School of Medicine, New York, NY; Neurology (K.I., M.T.), Kanagawa Children's Medical Center, Yokohama; Pediatrics (H.O.), Jichi Medical School, Tochigi, Japan; Experimental and Systems Pharmacology (K.M.G.), Washington State University, Spokane; and Molecular and Human Genetics (P.E.B.), Baylor College of Medicine, Houston, TX. phillip.pearl@childrens.harvard.edu.
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.
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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