Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucas...Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.展开更多
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 de...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.展开更多
目的探讨串联质谱(tandem mass spectrometry,MS/MS)筛查技术的应用,确定适用于贵州省部分地区新生儿高苯丙氨酸(phenylalanine,Phe)血症(gyperphenylalaninemia,HPA)的筛查指标Phe和Phe/酪氨酸(tyrosine,Tyr)的切值。方法选取贵州省新...目的探讨串联质谱(tandem mass spectrometry,MS/MS)筛查技术的应用,确定适用于贵州省部分地区新生儿高苯丙氨酸(phenylalanine,Phe)血症(gyperphenylalaninemia,HPA)的筛查指标Phe和Phe/酪氨酸(tyrosine,Tyr)的切值。方法选取贵州省新生儿疾病筛查中心99888名新生儿为研究对象,取足跟血制作血片,采用MS/MS技术检测Phe和Tyr并计算Phe/Tyr,采用多元线性回归方法及百分位数法确定血Phe和Phe/Tyr的切值。结果不同性别组新生儿血Phe水平比较,差异无统计学意义(P>0.05);不同胎龄新生儿血Phe水平之间存在差异(P<0.05),且<37周组低于≥37周组;除铜仁与黔东南、六盘水与黔东南外,其余地域间的新生儿血Phe值比较,差异均有统计学意义(P<0.05);在性别、胎龄和地域这3个因素中,地域对新生儿血Phe值的影响最大,不同性别组和胎龄组新生儿血Phe/Tyr值之间存在差异(P<0.05),且男>女、<37周组高于≥37周组;除铜仁与黔东南、黔西南与黔东南之间外,其余地域间新生儿血Phe/Tyr值比较、差异有统计学意义(P<0.05);在性别、胎龄和地域3个因素中,地域对新生儿血Phe/Tyr值的影响最大;综合性别、胎龄和地域因素,贵州省新生儿Phe MS/MS筛查切值定为109μmol/L,Phe/Tyr切值定为1.4。结论本研究确立了贵州省部分地区新生儿HPA血Phe及Phe/Tyr的筛查切值,可为筛查与诊断HPA提供重要的参考数据。展开更多
目的探讨河南地区使用全自动荧光免疫分析仪(Genetic Screening Processor,GSP)检测新生儿高苯丙氨酸血症(hyperphenylalaninemia,HPA)的筛查指标血苯丙氨酸(phenylalanine,Phe)水平时其参考限的建立。方法采用GSP分析仪和目前临床常规...目的探讨河南地区使用全自动荧光免疫分析仪(Genetic Screening Processor,GSP)检测新生儿高苯丙氨酸血症(hyperphenylalaninemia,HPA)的筛查指标血苯丙氨酸(phenylalanine,Phe)水平时其参考限的建立。方法采用GSP分析仪和目前临床常规使用的Victor2D 1420型荧光免疫分析仪(半自动分析仪)同步检测6204例新生儿血Phe水平并对其进行比较,使用百分位数法建立GSP分析仪筛查HPA时血Phe水平的参考限。结果 GSP分析仪和Victor2D 1420型荧光免疫分析仪对新生儿血Phe水平的检测结果呈显著正线性相关( r =0.393, P <0.001),但成对样本检测结果差异具有统计学意义( t =74.764, P <0.001);GSP分析仪检测血Phe水平时参考限为2.10 mg/dL。结论使用不同仪器设备检测血Phe水平时应分别建立其参考限;GSP分析仪检测时的参考限为2.10 mg/dL,以指导河南地区后续的HPA筛查工作。展开更多
文摘Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.
文摘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.
文摘目的探讨串联质谱(tandem mass spectrometry,MS/MS)筛查技术的应用,确定适用于贵州省部分地区新生儿高苯丙氨酸(phenylalanine,Phe)血症(gyperphenylalaninemia,HPA)的筛查指标Phe和Phe/酪氨酸(tyrosine,Tyr)的切值。方法选取贵州省新生儿疾病筛查中心99888名新生儿为研究对象,取足跟血制作血片,采用MS/MS技术检测Phe和Tyr并计算Phe/Tyr,采用多元线性回归方法及百分位数法确定血Phe和Phe/Tyr的切值。结果不同性别组新生儿血Phe水平比较,差异无统计学意义(P>0.05);不同胎龄新生儿血Phe水平之间存在差异(P<0.05),且<37周组低于≥37周组;除铜仁与黔东南、六盘水与黔东南外,其余地域间的新生儿血Phe值比较,差异均有统计学意义(P<0.05);在性别、胎龄和地域这3个因素中,地域对新生儿血Phe值的影响最大,不同性别组和胎龄组新生儿血Phe/Tyr值之间存在差异(P<0.05),且男>女、<37周组高于≥37周组;除铜仁与黔东南、黔西南与黔东南之间外,其余地域间新生儿血Phe/Tyr值比较、差异有统计学意义(P<0.05);在性别、胎龄和地域3个因素中,地域对新生儿血Phe/Tyr值的影响最大;综合性别、胎龄和地域因素,贵州省新生儿Phe MS/MS筛查切值定为109μmol/L,Phe/Tyr切值定为1.4。结论本研究确立了贵州省部分地区新生儿HPA血Phe及Phe/Tyr的筛查切值,可为筛查与诊断HPA提供重要的参考数据。
文摘目的探讨河南地区使用全自动荧光免疫分析仪(Genetic Screening Processor,GSP)检测新生儿高苯丙氨酸血症(hyperphenylalaninemia,HPA)的筛查指标血苯丙氨酸(phenylalanine,Phe)水平时其参考限的建立。方法采用GSP分析仪和目前临床常规使用的Victor2D 1420型荧光免疫分析仪(半自动分析仪)同步检测6204例新生儿血Phe水平并对其进行比较,使用百分位数法建立GSP分析仪筛查HPA时血Phe水平的参考限。结果 GSP分析仪和Victor2D 1420型荧光免疫分析仪对新生儿血Phe水平的检测结果呈显著正线性相关( r =0.393, P <0.001),但成对样本检测结果差异具有统计学意义( t =74.764, P <0.001);GSP分析仪检测血Phe水平时参考限为2.10 mg/dL。结论使用不同仪器设备检测血Phe水平时应分别建立其参考限;GSP分析仪检测时的参考限为2.10 mg/dL,以指导河南地区后续的HPA筛查工作。
