Application of isoxanthopterin as a new pterin marker in the differential diagnosis of hyperphenylalaninemia

摘要

Background 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.Methods 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.Results (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.Conclusions 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.