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
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.
Neurology. 2017 May 16;88(20):1919-1924. doi: 10.1212/WNL.0000000000003936. Epub 2017 Apr 14.
We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype.
Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil.
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.
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.
我们报告了一组10例γ-氨基丁酸（GABA）转氨酶缺乏症患者的病例系列，包括一项新的治疗试验和扩展的表型。
病例确诊、文献综述、综合评估以及使用氟马西尼进行长期治疗。
所有患者均表现为新生儿期或婴儿早期发作的脑病；其他特征包括肌张力减退、嗜睡、癫痫、舞蹈手足徐动症和线性生长加速。脑电图显示爆发抑制、改良高度节律失调、多灶性棘波和全身性棘慢波。10例患者中有5例目前存活，最后一次随访时年龄在18个月至9.5岁之间。2例患者接受了持续氟马西尼治疗。1例表型较轻的患者在21个月大时开始治疗，已持续20个月，警觉性提高，不自主运动减少。第2例患者表型更严重，开始使用氟马西尼时7岁，未持续使用。
GABA转氨酶缺乏症表现为新生儿期或婴儿期发作的脑病，包括嗜睡和舞蹈手足徐动症。与2岁前死亡相反，报告了更广泛的表型谱。GABA-A苯二氮䓬受体拮抗剂氟马西尼可能是一种治疗策略。
