Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype
Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype
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DOI：
10.1016/j.braindev.2021.07.002
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发表时间：
2021-10-29
影响因子：
1.7
通讯作者：
Okamoto, Nobuhiko
中科院分区：
文献类型：
--
作者：
Hasegawa, Yuiko;Nishi, Eriko;Okamoto, Nobuhiko
背景资料：芳香族L-氨基酸脱羧酶（AADC）缺乏症，由多巴脱羧酶（DDC）基因的致病性变体引起，是一种罕见的神经代谢紊乱，其中儿茶酚胺和5-羟色胺不能合成。从大量的报告中，人们已经认识到，大多数受影响的患者在卧床不起的状态下表现出严重的发育迟缓，并且不能说话。另一方面，已经报道了具有AADC缺陷的轻度表型的患者，但他们的数量仅为少数病例。因此，该疾病的表型的变化似乎是广泛的，它可能是具有挑战性的诊断为AADC deficiency.Case报告：我们报告的DDC（c.202G > A和c.254C > T）在两个姐妹篇，其主要投诉是轻度发育迟缓，通过全外显子组测序（WES）的新的复合杂合变异。此外，我们描述了它们的临床特征，并提供了一个图像，显示了位于不同位点的变体，负责催化AADC的三维结构。诊断后，患者被规定的单胺氧化酶（MAO）inhibitors.Interpretation：我们的病例表明，一个全面的基因组方法有助于诊断AADC缺乏症的非典型特征，并强调了解这种疾病的诊断和适当的治疗的变化的意义。(C)2021年日本儿童神经病学学会。Elsevier B. V.出版，保留所有权利。
Background: Aromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case report: We report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.Interpretation: Our cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment. (C) 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.