Novel SPR mutation in first Chinese patient with sepiapterin reductase deficiency: urinary biomarker validation in oldest treated case.

Background: Sepiapterin reductase deficiency (SRD) is a rare disorder characterized by motor and cognitive symptoms, where early diagnosis and treatment can significantly improve patient outcomes.

Methods: We performed genetic analysis, functional studies including Western blot and immunocytochemistry, and urinary sepiapterin measurements in a Chinese patient presenting with levodopa-responsive dystonia and parkinsonism.

Results: We identified a novel homozygous mutation (c.380 A > T, p.N127I) in the SPR gene. Functional studies demonstrated reduced expression of the mutant protein while maintaining normal subcellular localization, confirming its pathogenicity. Additionally, we detected elevated urinary sepiapterin levels in this patient, who represents the oldest documented case receiving levodopa treatment.

Conclusions: This study not only expands the genetic spectrum of SRD but also validates the utility of urinary sepiapterin as a reliable, non-invasive diagnostic biomarker, even in older treated patients.