Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency
Simultaneous assay of urine sepiapterin and creatinine in patients with sepiapterin reductase deficiency
复制标题
墨蝶呤还原酶缺乏症患者尿液墨蝶呤和肌酐的同步测定
DOI：
10.1016/j.cca.2022.07.016
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发表时间：
2022
期刊：
影响因子：
5
通讯作者：
Kobayashi K
中科院分区：
文献类型：
--
作者：
Hyodo Y;Akiyama T;Fukuyama T;Mimaki M;Watanabe K;Kumagai T;Kobayashi K
Sepiapterin reductase deficiency（SRD）是由于Sepiapterin reductase在四氢生物蝶呤的生物合成中起重要作用，导致多巴胺和5-羟色胺缺乏而引起中枢神经系统症状。由于缺乏高苯丙氨酸血症，新生儿筛查无法检测到SRD。为了从生物化学上诊断SRD，认为有必要确认脑脊液（CSF）中单胺代谢物减少和sepiapterin升高，因为过去的研究显示尿sepiapterin没有升高。然而，最近，升高尿sepiapterin在SRD.MethodsWe开发了一种快速的方法来测量sepiapterin和肌酐同时使用高效液相色谱荧光和紫外检测。在3例SRD患者、2例SRD携带者、4例SRD同胞和103例非SRD patients.Results3例SRD患者中，尿sepiapterin浓度分别为1086、914和575 μmol/mol肌酐（上限：101.7 μmol/mol肌酐），显著高于其他组。1例SRD患者同时测定了脑脊液中的Sepiapterin浓度，其值为4.1nmol/L（上限为0.5nmol/L）。该测定系统还可用于测量CSF中的墨蝶呤。
ObjectivesSepiapterin 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.MethodsWe 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.ResultsIn 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).ConclusionsThe 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.