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.

中文翻译：

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芳香族 L-氨基酸脱羧酶缺乏症的新变异：轻度表型姐妹的病例报告

背景

由多巴脱羧酶 (DDC) 基因的致病性变异引起的芳香族 L-氨基酸脱羧酶 (AADC) 缺乏症是一种罕见的神经代谢疾病，其中儿茶酚胺和血清素不合成。从大量报道中可以看出，大多数受影响的患者在卧床状态下表现出严重的发育迟缓，无法说话。另一方面，已经报道了具有 AADC 缺乏的轻度表型的患者，但他们的病例数很少。因此，该疾病表型的变异似乎很广泛，将非典型表型诊断为 AADC 缺乏症可能具有挑战性。

案例报告

我们通过全外显子组测序 (WES) 报告了两个姐妹的DDC（c.202G > A 和 c.254C > T）中的新型复合杂合变体，其主要抱怨是轻度发育迟缓。此外，我们描述了它们的临床特征并提供了一张图像，显示了位于不同位点的变异体，这些变异体在三维结构中负责催化 AADC。患者在诊断后被开具单胺氧化酶 (MAO) 抑制剂。

解释

我们的案例表明，综合基因组方法有助于诊断具有非典型特征的 AADC 缺乏症，并强调了解这种疾病的变异对于诊断和适当治疗的重要性。