Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency.

Abstract

OBJECTIVES:

Sepiapterin reductase deficiency (SRD) causes central nervous system symptoms due to dopamine and serotonin depletion because sepiapterin reductase plays an important role in tetrahydrobiopterin biosynthesis. SRD cannot be detected by newborn screening because of the absent hyperphenylalaninemia. To diagnose SRD biochemically, confirmation of reduced monoamine metabolites and elevated sepiapterin in the cerebrospinal fluid (CSF) has been considered necessary, because a past study showed no elevation of urine sepiapterin. Recently, however, the elevation of urine sepiapterin in SRD was reported.

METHODS:

We developed a fast method to measure sepiapterin and creatinine simultaneously using high-performance liquid chromatography with fluorescence and ultraviolet detection. Urine sepiapterin and creatinine were measured in three SRD patients, two SRD carriers, four SRD siblings, and 103 non-SRD patients.

RESULTS:

In the three SRD cases, concentrations of urine sepiapterin were 1086, 914, and 575 µmol/mol creatinine (upper limit: 101.7 µmol/mol creatinine), and were markedly higher than those in other groups. CSF sepiapterin concentration was also measured in one SRD case and it was 4.1 nmol/L (upper limit: 0.5 nmol/L).

CONCLUSIONS:

The simultaneous determination of urine sepiapterin and creatinine appears helpful for the diagnosis of SRD. This assay system can also be used to measure sepiapterin in the CSF.

• Authors: Yuki Hyodo, Tomoyuki Akiyama, Tetsuhiro Fukuyama, Masakazu Mimaki, Keiko Watanabe, Tadayuki Kumagai, Katsuhiro Kobayashi
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 534 Pg. 167-172 (Sep 01 2022) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 35926683 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Pterins
• Creatinine
• sepiapterin

Topics

• Creatinine
• Dystonia (diagnosis)
• Humans
• Infant, Newborn
• Metabolism, Inborn Errors
• Psychomotor Disorders
• Pterins (metabolism)