Prevalence of Aromatic L-Amino Acid Decarboxylase Deficiency in At-Risk Populations
Prevalence of Aromatic L-Amino Acid Decarboxylase Deficiency in At-Risk Populations
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DOI：
10.1016/j.pediatrneurol.2019.11.022
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发表时间：
2020-05-01
影响因子：
3.8
通讯作者：
Reott, Michael
中科院分区：
文献类型：
--
作者：
Hyland, Keith;Reott, Michael
背景：芳香族I-氨基酸脱羧酶(AADC)缺乏症是一种常染色体隐性遗传性代谢紊乱，由多巴脱羧酶(DDC)基因的致病变异引起。从婴儿期起，大脑中多巴胺和5-羟色胺产生的丧失阻碍了运动发育里程碑的实现。方法：我们回顾评估了医学神经遗传学实验室要求分析脑脊液中的神经递质代谢物、血浆中AADC酶活性和/或DDC基因的Sanger测序所获得的数据。我们的主要目标是评估AADC缺乏症在高危人群中的患病率。结果：在8年的研究期间，收到了大约20,000份脑脊液样本，要求进行神经递质代谢物分析；22例AADC缺乏症样本检测呈阳性，基于5-羟基吲哚乙酸和高香草酸浓度的降低，以及3-0-甲基多巴的增加，估计患病率约为0.112%，或1：900。在收到的81份血浆AADC酶分析请求中，有25份样本的血浆AADC活性极低，与AADC缺乏症一致，因此又发现了9例。通过Sanger测序，共有另外5名患者被确定为导致AADC缺陷诊断的主要要求。结论：总体而言，这些分析确定了36例新的AADC缺陷病例。测序结果表明，26个不同的DDC基因变异体具有很大的多样性；其中5个以前没有与AADC缺乏症相关。本研究的结果与新出现的文献以及对AADC缺乏症的流行病学和遗传学的理解相一致。(C)2020作者。由爱思唯尔公司出版。
Background: Aromatic I.-amino acid decarboxylase (AADC) deficiency is an autosomal recessive metabolic disorder that results from disease-causing pathogenic variants of the dopa decarboxylase (DDC) gene. Loss of dopamine and serotonin production in the brain from infancy prevents achievement of motor developmental milestones.Methods: We retrospectively evaluated data obtained from requests to Medical Neurogenetics Laboratories for analyses of neurotransmitter metabolites in the cerebrospinal fluid, AADC enzyme activity in plasma, and/or Sanger sequencing of the DDC gene. Our primary objective was to estimate the prevalence of AADC deficiency in an at-risk population.Results: Approximately 20,000 cerebrospinal fluid samples were received with a request for neurotransmitter metabolite analysis in the eight-year study period; 22 samples tested positive for AADC deficiency based on decreased concentrations of 5-hydroxyindoleacetic acid and homovanillic acid, and increased 3-0-methyldopa, establishing an estimated prevalence of approximately 0.112%, or 1:900. Of the 81 requests received for plasma AADC enzyme analysis, 25 samples had very low plasma AADC activity consistent with AADC deficiency, resulting in identification of nine additional cases. A total of five additional patients were identified by Sanger sequencing as the primary request leading to the diagnosis of AADC deficiency.Conclusions: Overall, these analyses identified 36 new cases of AADC deficiency. Sequencing findings showed substantial diversity with identification of 26 different DDC gene variants; five had not previously been associated with AADC deficiency. The results of the present study align with the emerging literature and understanding of the epidemiology and genetics of AADC deficiency. (C) 2020 The Authors. Published by Elsevier Inc.