Year: 2024
Type: article
Study design: Case Report
Abstract: 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.
Source: PEDIATRICS
Authors: Jiaqing Li, Sanqing Xu
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4404506984