Application of isoxanthopterin as a new pterin marker in the differential diagnosis of hyperphenylalaninemia
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This study aimed to explore the value of applying a new pterin marker (isoxanthopterin) to the traditional urine pterin analysis to reduce the rate of mis-diagnosis of 6-pyruvoyltetrahydropterin synthase deficiency (PTPSD) and improve the accuracy of diagnosis.
We compared the urine neopterin (N), biopterin (B), isoxanthopterin (Iso), B% and Iso% levels between patients with phenylalanine hydroxylase deficiency and those with PTPSD, and found the most specific pterin biomarkers by ROC analysis. A positive cut-off value of urine pterins was determined. The effect of combined Iso% + B + B% in reducing PTPSD mis-diagnosis was evaluated, and the different urine pterin levels in PTPSD and false PTPSD (FPTPSD) were compared. The concordance of PTPSD diagnosis by the new pterin scheme and gene mutation analysis was determined.
(1) Urinary B, B%, Iso and Iso% were significantly lower in PTPSD than those in phenylalanine hydroxylase-deficiency group (P < 0.01); (2) Iso%, B%, and B were the most specific markers; (3) The positive cut-off values of B, B%, Iso% for PTPSD were < 0.17 mmoL/moLCr, < 5.0%, and < 9.5%, respectively; (4) urinary B + B% + Iso% scheme significantly reduced the false-positive rate of PTPSD compared to traditional ones. The Iso% levels in FPTPSD group were higher than the ones in PTPSD group; (5) an accuracy of diagnosis for PTPSD was increased by 9–19% when Iso% was introduced to urinary pterin scheme.
Iso% is helpful to reduce the rate of misdiagnosis of PTPSD in the diagnosis by urinary pterin analysis for hyperphenylalaninemias and improve the accuracy of diagnosis. This approach is worthy of further development and increased utilization.
Keywords6-Pyruvoyltetrahydropterin synthase Hyperphenylalaninemia Isoxanthopterin Phenylalanine hydroxylase Pterin
PZB contributed to HPLC performance of the samples, statistic analysis of the data, and drafting of the article. JY contributed to conception and design, acquisition and interpretation of data, and participate in drafting of the article. LSH, WJQ, HWZ, XFG contributed to acquisition of the samples and patients’ information. YGY contributed to acquisition of the samples and patients’ information, and the gene verification and analysis for the sample. JGW contributed to the gene verification and analysis for the sample. All authors gave their approval for the final version to be published.
This study was supported by the National Key Research and Development Program of China (2016YFC0905100 and 2016 YFC901505).
Compliance with ethical standards
This study was approved by the Ethics Committee of Xinhua Hospital (no. XHEC-D-2018-021).
Conflict of interest
No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.
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