Background:Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-synthase deficiency).Newborn screening for classica...Background:Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-synthase deficiency).Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.Methods:A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine,methionine-phenylalanine-ratio and propionylcarnitine as second-tiers.Proposed cnt-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B12 deficiency from Qatar and Germany.Results:Over a 12 months period,the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%,while allowing for additional systematic inclusion of remethylation disorders and vitamin B12 deficiency into the screening panel for Qatar.In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B12 deficiency and one patient with an isolated remethylation disorder.Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B12 deficiency showed that all of these patients would have been detected by the cutoffs used in the proposed new strategy.In addition,an adapted strategy for Germany using methionine,methionine-phenylalanine-ratio and propionylcarnitine as first-tier,and homocysteine as a second-tier test was also positively evaluated retrospectively.Conclusions:The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B12 deficiency in the screening panel,while lowering the reca展开更多
目的观察蛋氨酸(methionine,Met)负载对大鼠肝细胞同型半胱氨酸代谢酶及相关化合物的影响。方法体外培养BRL(Baffalo rat liver)细胞,将其分为两组,对照组和Met组(20 mmol/L Met作用1h)。采用高效液相色谱法检测同型半胱氨酸(Hcy)、半...目的观察蛋氨酸(methionine,Met)负载对大鼠肝细胞同型半胱氨酸代谢酶及相关化合物的影响。方法体外培养BRL(Baffalo rat liver)细胞,将其分为两组,对照组和Met组(20 mmol/L Met作用1h)。采用高效液相色谱法检测同型半胱氨酸(Hcy)、半胱氨酸(Cys)、谷胱甘肽(GSH)、S-腺苷蛋氨酸(SAM)、S-腺苷同型半胱氨酸(SAH)含量,全自动氨基酸分析仪检测培养液中丝氨酸(Ser)、谷氨酸(Glu)、甘氨酸(Gly)、胱氨酸(Cys)、牛磺酸(Tau)的含量,参照文献方法检测细胞内S-腺苷同型半胱氨酸水解酶(SAHH)、胱硫醚-β-合成酶(CBS)、甜菜碱同型半胱氨酸甲基转移酶(BHMT)和蛋氨酸合成酶(MS)的活性。结果蛋氨酸负载后,培养液中Hcy、Cys、Ser和胱氨酸含量显著增加(P<0.05),而Glu、Gly和Tau含量显著减少(P<0.05);细胞内SAM含量显著增加(P<0.05),SAHH活性显著增强(P<0.05),BHMT和MS活性显著减弱(P<0.05)。SAH含量和CBS活性变化不明显。结论蛋氨酸负载可活化大鼠肝细胞中同型半胱氨酸的转硫化途径,同时抑制其再甲基化途径。展开更多
文摘Background:Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-synthase deficiency).Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.Methods:A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine,methionine-phenylalanine-ratio and propionylcarnitine as second-tiers.Proposed cnt-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B12 deficiency from Qatar and Germany.Results:Over a 12 months period,the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%,while allowing for additional systematic inclusion of remethylation disorders and vitamin B12 deficiency into the screening panel for Qatar.In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B12 deficiency and one patient with an isolated remethylation disorder.Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B12 deficiency showed that all of these patients would have been detected by the cutoffs used in the proposed new strategy.In addition,an adapted strategy for Germany using methionine,methionine-phenylalanine-ratio and propionylcarnitine as first-tier,and homocysteine as a second-tier test was also positively evaluated retrospectively.Conclusions:The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B12 deficiency in the screening panel,while lowering the reca
文摘目的观察蛋氨酸(methionine,Met)负载对大鼠肝细胞同型半胱氨酸代谢酶及相关化合物的影响。方法体外培养BRL(Baffalo rat liver)细胞,将其分为两组,对照组和Met组(20 mmol/L Met作用1h)。采用高效液相色谱法检测同型半胱氨酸(Hcy)、半胱氨酸(Cys)、谷胱甘肽(GSH)、S-腺苷蛋氨酸(SAM)、S-腺苷同型半胱氨酸(SAH)含量,全自动氨基酸分析仪检测培养液中丝氨酸(Ser)、谷氨酸(Glu)、甘氨酸(Gly)、胱氨酸(Cys)、牛磺酸(Tau)的含量,参照文献方法检测细胞内S-腺苷同型半胱氨酸水解酶(SAHH)、胱硫醚-β-合成酶(CBS)、甜菜碱同型半胱氨酸甲基转移酶(BHMT)和蛋氨酸合成酶(MS)的活性。结果蛋氨酸负载后,培养液中Hcy、Cys、Ser和胱氨酸含量显著增加(P<0.05),而Glu、Gly和Tau含量显著减少(P<0.05);细胞内SAM含量显著增加(P<0.05),SAHH活性显著增强(P<0.05),BHMT和MS活性显著减弱(P<0.05)。SAH含量和CBS活性变化不明显。结论蛋氨酸负载可活化大鼠肝细胞中同型半胱氨酸的转硫化途径,同时抑制其再甲基化途径。
