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Two Greek siblings with sepiapterin reductase deficiency
Marcel M Verbeek1, Michel A A P Willemsen2, Ron A Wevers1
1Department of Neurology, Laboratory of Pediatrics and Neurology, 830 LKN, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Molecular Genetics and Metabolism
|May 27, 2008
Summary
Sepiapterin reductase deficiency, a rare neurotransmitter disorder, is diagnosed by measuring sepiapterin in cerebrospinal fluid (CSF) and observing low urinary metabolites. Early diagnosis aids L-dopa treatment response.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Sepiapterin reductase (SR) deficiency is a rare inherited disorder affecting neurotransmitter metabolism.
- Fewer than 25 cases have been documented globally.
Purpose of the Study:
- To detail the clinical presentation and diagnostic findings in two Greek siblings with SR deficiency.
- To highlight key biomarkers for accurate diagnosis and management.
Main Methods:
- Clinical history review and comprehensive cerebrospinal fluid (CSF) and urine analysis.
- Enzyme activity assays in cultured fibroblasts and mutation analysis of the SPR gene.
- Quantification of neurotransmitter metabolites, neopterin, biopterin, and sepiapterin.
Main Results:
- Patients presented with a progressive, L-dopa responsive movement disorder.
- CSF showed very low homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG).
- Abnormally high CSF sepiapterin and undetectable 5-hydroxytryptophan were noted; fibroblasts lacked SR enzyme activity; a homozygous SPR gene mutation (K251X) was identified.
Conclusions:
- Accurate SR deficiency diagnosis relies on CSF sepiapterin quantification, alongside HVA and 5-HIAA.
- Abnormal urinary neurotransmitter metabolites can indicate SR deficiency prior to CSF analysis.
- The study reaffirms the significant clinical benefit of L-dopa treatment in SR deficiency.
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