Dried blood spot (DBS) monitoring of Nitisinone (NTBC) and succinylacetone (SA) in hereditary tyrosinaemia type 1 (HT1) patients is not widely available in the United Kingdom. Currently biochemical monitoring utilises urinary SA, blood spot tyrosine (Tyr) and phenylalanine (Phe) monitoring which can lack in convenience and accuracy respectively. We report the development of a DBS assay for NTBC and SA and analysed retrospective clinical and biochemical data for HT1 patients from a single UK centre over a 6-year period. A total of 13 HT1 patients were evaluated. Eleven presented with liver dysfunction (2 with associated renal tubulopathy) and 2 were detected by early sibling screening. All patients (age 0.03 - 22 months) were commenced on a Tyr / Phe restricted diet and NTBC at diagnosis. Ten patients were on twice daily dosing and 3 were on single daily dosing at the start of monitoring. One patient from each dosing group swapped between dosing regimens at 20 years of age and 8 months of age respectively. A total of 684 DBS samples were analysed; 80% of NTBC concentrations were between 9.2-27umol/L when SA was <0.3umol/L. Patients on twice daily dosing regimens had significantly higher NTBC concentration compared to those on once daily dosing (p<0.0001). The median dose required in the twice daily doing group was significantly lower when compared to once daily dosing. DBS monitoring for NTBC and SA concentrations in HT1 patients is a rapid and convenient method which allows physicians to individualise treatment plans and observe adherence to treatment.

在英国，尚未广泛监测1型遗传性酪氨酸血症（HT1）患者的Nitisinone（NTBC）和琥珀酰丙酮（SA）的干血斑（DBS）。当前的生化监测利用尿SA，血点酪氨酸（Tyr）和苯丙氨酸（Phe）监测，它们分别缺乏便利性和准确性。我们报告了NTBC和SA的DBS分析的发展情况，并分析了在6年内来自单个英国中心的HT1患者的回顾性临床和生化数据。总共评估了13例HT1患者。通过早期同胞筛查发现了11例肝功能不全（2例伴有肾小管病）和2例。所有患者（年龄0.03-22个月）在诊断时开始接受Tyr / Phe限制饮食和NTBC。监测开始时，有10名患者每天两次给药，而3名每天一次给药。每个给药组的一名患者分别在20岁和8个月大时更换给药方案。总共分析了684个DBS样本。当SA <0.3umol / L时，NTBC浓度的80％在9.2-27umol / L之间。每天两次给药方案的患者与每天一次给药的患者相比，NTBC浓度显着更高（p <0.0001）。与每日一次给药相比，每日两次给药组所需的中位剂量显着降低。DBS监测HT1患者中NTBC和SA的浓度是一种快速便捷的方法，可让医生个性化治疗计划并观察治疗依从性。每个给药组的一名患者分别在20岁和8个月大时更换给药方案。总共分析了684个DBS样本。当SA <0.3umol / L时，NTBC浓度的80％在9.2-27umol / L之间。每天两次给药方案的患者与每天一次给药的患者相比，NTBC浓度明显更高（p <0.0001）。与每日一次给药相比，每日两次给药组所需的中位剂量明显降低。DBS监测HT1患者中NTBC和SA的浓度是一种快速便捷的方法，可让医生个性化治疗计划并观察治疗依从性。每个给药组的一名患者分别在20岁和8个月大时更换给药方案。总共分析了684个DBS样本。当SA <0.3umol / L时，NTBC浓度的80％在9.2-27umol / L之间。每天两次给药方案的患者与每天一次给药的患者相比，NTBC浓度明显更高（p <0.0001）。与每日一次给药相比，每日两次给药组所需的中位剂量显着降低。DBS监测HT1患者中NTBC和SA的浓度是一种快速便捷的方法，可让医生个性化治疗计划并观察治疗依从性。当SA <0.3umol / L时为2-27umol / L。每天两次给药方案的患者与每天一次给药的患者相比，NTBC浓度显着更高（p <0.0001）。与每日一次给药相比，每日两次给药组所需的中位剂量明显降低。DBS监测HT1患者中NTBC和SA的浓度是一种快速便捷的方法，可让医生个性化治疗计划并观察治疗依从性。当SA <0.3umol / L时为2-27umol / L。每天两次给药方案的患者与每天一次给药的患者相比，NTBC浓度显着更高（p <0.0001）。与每日一次给药相比，每日两次给药组所需的中位剂量显着降低。DBS监测HT1患者中NTBC和SA的浓度是一种快速便捷的方法，可让医生个性化治疗计划并观察治疗依从性。