Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts.
Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington.
Ann Clin Transl Neurol. 2018 Dec 3;6(1):114-120. doi: 10.1002/acn3.696. eCollection 2019 Jan.
Succinic Semialdehyde Dehydrogenase (SSADH) deficiency is a disorder of elevated gamma-amino butyric acid (GABA) and gamma hydroxybutyric acid (GHB) and a complex neuropsychiatric profile. Adult reports suggest worsening epilepsy and high SUDEP risk.
Subjects with confirmed SSADH deficiency were recruited into a longitudinal study. Plasma thyroid hormone and total GABA/GHB were quantified by standard clinical chemistry methodologies and mass spectrometry, respectively.
A total of 133 subjects with SSADH deficiency are enrolled in the registry; 49 participated in the longitudinal study. The age range of the population is 8 weeks to 63 years (median 7.75 year; 44% male). There is a significant difference in proportions among the age groups in subjects affected with hypotonia, compulsive behavior, sleep disturbances, and seizures. Epilepsy is present in 50% of the total population, and more prevalent in subjects 12 years and older ( = 0.001). The median age of onset for absence seizures was 2 years, and 12 years for generalized tonic-clonic seizures ( < 0.01). The SUDEP rate in adults was 12% (4/33). There was a significant age-dependent negative correlation between GABA and T levels.
There is an age-dependent association with worsening of epilepsy, behavioral disturbances including obsessive-compulsive behavior, and sleep disturbances with age in SSADH deficiency. There is a high risk of SUDEP. We have observed more absence seizures in younger patients, compared to tonic-clonic in the older cohort, which correlates with age-related changes in GABA and GHB concentration and thyroid function, as well as the natural history of seizures in the murine model.
琥珀酸半醛脱氢酶（SSADH）缺乏症是一种γ-氨基丁酸（GABA）和γ-羟基丁酸（GHB）升高的疾病，伴有复杂的神经精神表现。成人报道表明癫痫恶化和高 SUDEP 风险。
确诊为 SSADH 缺乏症的受试者被招募到一项纵向研究中。通过标准临床化学方法和质谱法分别定量测定血浆甲状腺激素和总 GABA/GHB。
共有 133 例 SSADH 缺乏症患者登记入该注册中心；其中 49 例参加了纵向研究。该人群的年龄范围为 8 周至 63 岁（中位数为 7.75 岁；44%为男性）。在患有肌张力低下、强迫行为、睡眠障碍和癫痫的受试者中，年龄组之间的比例存在显著差异。50%的总人群患有癫痫，12 岁及以上的患者更为常见（=0.001）。失神发作的中位发病年龄为 2 岁，全面强直阵挛发作的中位发病年龄为 12 岁（<0.01）。成人的 SUDEP 发生率为 12%（4/33）。GABA 和 T 水平呈年龄依赖性负相关。
SSADH 缺乏症患者的癫痫、行为障碍（包括强迫行为）和睡眠障碍随年龄的增长而恶化，SUDEP 的风险较高。我们观察到较年轻的患者中失神发作较多，而年长的患者中强直阵挛发作较多，这与 GABA 和 GHB 浓度及甲状腺功能的年龄相关性变化以及在鼠模型中的癫痫自然史有关。
