BACKGROUND Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder with heterogeneous phenotypic spectrum resulting from disease-causing variants in the dopa decarboxylase (DDC) gene. Consensus guidelines recommend dopamine agonists, monoamine oxidase inhibitors, and other symptomatic treatments, but most patients have an unrelenting disease course with no response to these therapies. CASE PRESENTATION We describe 2 African American siblings with AADC deficiency and identify 2 DDC gene variants not previously associated with the disorder. The patients were evaluated for cognitive and neurologic impairments. Diagnosis of AADC deficiency was initially based on evaluation of urine and plasma metabolites, followed by targeted DDC gene sequencing. The first patient, a firstborn African American female, had moderate elevations of vanillactic and vanilpyruvic acids, and slight elevation of N-acetylvanilalanine in urine. The second patient, an African American female and younger sibling of the first patient, had low AADC enzyme activity and elevated 3-O-methyldopa levels in plasma. Genetic testing confirmed that both siblings possessed the same 2 DDC gene variants, which were identified as NM_000790.3: c.48C > A (p.Tyr16Ter) and NM_000790.3: c.116G > C (p.Arg39Pro). CONCLUSIONS This report describes 2 previously unknown patients with AADC deficiency and confirmed the presence of 2 DDC gene variants not previously associated with this disorder. Further research is needed to identify disease-modifying treatments for this devastating neurometabolic disorder. Gene therapy with a recombinant adeno-associated viral vector serotype 2 carrying the gene for the human AADC protein (AAV2-hAADC) is currently in clinical development.

中文翻译：

---

病例报告：在2个非裔美国同胞中发现2种芳香L-氨基酸脱羧酶缺乏症的基因变异。

背景技术芳香族L-氨基酸脱羧酶（AADC）缺乏症是一种罕见的遗传疾病，具有异质表型谱，这是由多巴脱羧酶（DDC）基因的致病变异引起的。共识性指南建议使用多巴胺激动剂，单胺氧化酶抑制剂和其他对症治疗，但是大多数患者的病程不减，对这些疗法无反应。病例介绍我们描述了2个患有AADC缺乏症的非洲裔美国兄弟姐妹，并鉴定了2种以前与该疾病无关的DDC基因变异。对患者进行了认知和神经功能障碍评估。AADC缺乏症的诊断最初是基于尿液和血浆代谢物的评估，然后进行靶向DDC基因测序。第一位患者，一位长子非裔女性，尿液中的香草酸和香草丙酮酸含量适度升高，N-乙酰香草醛含量略有升高。第二名患者是一名非洲裔美国女性，第一名患者的年轻同胞，其AADC酶活性低，血浆中3-O-甲基多巴水平升高。基因测试证实两个兄弟姐妹都拥有相同的2个DDC基因变体，分别被识别为NM_000790.3：c.48C> A（p.Tyr16Ter）和NM_000790.3：c.116G> C（p.Arg39Pro）。结论该报告描述了2名先前未知的AADC缺乏症患者，并证实存在2种DDC基因变体，这些变体先前与该疾病无关。需要进一步的研究来确定这种破坏性神经代谢疾病的疾病缓解疗法。