目的:探讨临床特点,ALDH5A1基因变异,治疗,琥珀酸半醛脱氢酶(SSADH)缺乏症患者的预后。
方法:这项回顾性研究评估了2013年9月至2023年9月北京大学第一医院儿科收治的13例SSADH缺乏症患者的发现。
结果:13例患者(男性7例,女性6例,兄弟姐妹2例)有1个月至1岁的症状。他们的尿液4-羟基丁酸水平升高,并伴有血清乳酸水平轻度升高。脑磁共振成像(MRI)显示苍白球两侧及其他区域对称异常信号。13例患者均有精神运动性迟钝,七个人出现癫痫发作。在这13名患者中鉴定的ALDH5A1基因的18种变体中,以前有6个报道,而12个是新的变体。在12个新的变体中,三(c.85_116del,c.206_222dup,c.762C>G)是致病性变异;五种(c.427delA,c.515G>A,c.637C>T,c.755G>T,c.1274T>C)可能是致病性的;其余四个(c.454G>C,c.479C>T,c.1480G>A,c.1501G>C)是意义不确定的变体。患者接受了左旋肉碱等药物,vigabatrin,和牛磺酸,同时对症治疗。他们的尿液4-羟基丁酸水平显示出不同程度的降低。
结论:分析了13例早发性SSADH缺乏症患者的队列。症状发生在1个月至1岁之间。鉴定了ALDH5A1基因的12种新变体。
OBJECTIVE: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency.
METHODS: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023.
RESULTS: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction.
CONCLUSIONS: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.