Juvenile parkinsonism is an exceedingly rare condition in which clinical signs of parkinsonism manifest before 21 years of age. Although the genetic underpinnings of this disorder are increasingly recognized, the full range of inherited metabolic contributors remains undefined. We present the first case of levodopa-responsive juvenile parkinsonism associated with dihydropyrimidinase deficiency caused by a novel DPYS variant. A 13-year-old patient presented with rapid progression of dysphagia, dysarthria, and loss of ambulation over 18 months. Whole-exome sequencing revealed compound heterozygous variants in the DPYS gene (NM_001385: c.1393C>T, p.R465X, and c.905G>A, p.R302Q). In silico analysis predicted both variants to be pathogenic. Further urinary metabolome analysis demonstrated markedly elevated dihydrouracil and dihydrothymine levels, confirming impaired pyrimidine metabolism. Levodopa treatment effectively relieved the patient's motor symptoms. This report identifies DPYS as a novel genetic cause of juvenile parkinsonism and underscores the potential efficacy of levodopa therapy in managing motor dysfunction in DYPS-related parkinsonism.

中文翻译：

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与二氢嘧啶酶缺乏症相关的青少年帕金森病。


青少年帕金森病是一种极其罕见的疾病，其中帕金森病的临床体征在 21 岁之前出现。尽管这种疾病的遗传基础越来越得到认可，但遗传代谢因素的全部范围仍未确定。我们提出了第一例与新型 DPYS 变体引起的二氢嘧啶酶缺乏症相关的左旋多巴反应性青少年帕金森病病例。一名 13 岁患者在 18 个月内出现吞咽困难、构音障碍和行走能力的快速进展。全外显子组测序揭示了 DPYS 基因中的复合杂合变异 （NM_001385： c.1393C>T， p.R465X 和 c.905G>A， p.R302Q）。计算机分析预测这两种变体都是致病性的。进一步的尿液代谢组分析显示二氢尿嘧啶和二氢胸腺嘧啶水平显著升高，证实嘧啶代谢受损。左旋多巴治疗有效缓解了患者的运动症状。本报告将 DPYS 确定为青少年帕金森病的新遗传原因，并强调了左旋多巴治疗在 DYPS 相关帕金森病运动功能障碍方面的潜在疗效。