Use of a home phenylalanine meter to help manage PKU

苯丙氨酸羟化酶（PAH）缺乏症，传统上称为苯丙酮尿症（PKU），导致 苯丙氨酸（PHE）在受影响个体的血液中的积累，是 基于人口的新生儿筛查苯丙酮尿症的早期诊断及饮食治疗 防止神经系统的破坏，但神经发育和心理问题是定期诊断 即使是在早期发现并持续治疗的患者中。美国医学遗传学学会 和基因组学（ACMG）最近发表了一份临床治疗指南，认识到生活的困难- 长期遵守治疗方案的指南报告说，几乎所有的青少年和成年人都有 血液PHE水平超出推荐的治疗范围，导致执行功能减弱 以及其他神经和神经精神问题。为了改善PKU患者的预后，ACMG指南 注意到，并倡导，“需要更好的工具和策略来优化对个人的护理， 长期成果”。此外，全国PKU联盟，在美国领先的病人倡导组织， PKU患者，已经使现场护理PHE仪的开发成为其头号研究重点。 为了响应更好的工具来优化PKU患者护理的呼吁，Baebies团队正在开发 FINDER™数字微流体系统用于家庭PHE测量。我们的团队将调查 使用FINDER™设备改进PHE水平测试程序的重要性。我们假设 方便和准确的家庭PHE监测的可用性将提高PHE监测的频率， PKU患者，这将导致更好的PHE控制。预期成果包括： 降低PHE水平，更好的实时PHE控制，以及开发手持式PHE的临床依据 设备在未来。具体目标1是通过比较PHE，在临床上验证FINDERTM PHE检测试剂盒 器械上获得的结果与标准临床实验室测定的结果。我们将使用废弃的 来自匹兹堡儿童医院PKU诊所患者的全血样本， 临床相关范围为60 - 1，200 μ mol/L。我们假设使用FINDERTM获得的水平将 等同于使用标准技术在临床上测量的那些。具体目标2是测试 我们的微流体装置在家庭环境中的应用。具体目标2a是提供FINDER™的实践培训 在受控临床环境中使用器械。具体目标2b是召集焦点小组，以优化家庭用户 接口和评估培训材料。具体目标3是证明， 在降低患者PHE水平方面，家庭将比类似的频繁接触方案更有效， 同时测量PHE水平。因此，该项目不仅将建立技术能力， 我们的PHE监测系统，但也将该系统纳入慢性PKU的常规护理的有效性 疾病管理。

Phenylalanine hydroxylase (PAH) deficiency, traditionally known as phenylketonuria (PKU), results in accumulation of phenylalanine (PHE) in the blood of affected individuals and was the original motivation for population-based newborn screening. Early identification of PKU and dietary treatment for PKU patients prevent neurological devastation, but neurodevelopmental and psychological problems are regularly diagnosed even in patients who are identified early and treated continuously. The American College of Medical Genetics and Genomics (ACMG) recently published a clinical treatment guideline that recognizes the difficulty of life- long compliance to therapeutic regimens The guideline reports that nearly all adolescents and adults have blood PHE levels that are out of the recommended therapeutic range, leading to diminished executive function and other neurologic and neuropsychiatric problems. To improve PKU patient outcomes, the ACMG guideline notes, and advocates, “better tools and strategies are required to optimize care for the individual and improve long-term outcomes.” Moreover, the National PKU Alliance, the leading patient advocacy group in the U.S. for patients with PKU, has made development of a point of care PHE meter its number one research priority. In answering the call for better tools to optimize PKU patient care, the Baebies team is developing the FINDER™ digital microfluidic system for home PHE measurements. Our team will investigate the clinical significance of using the FINDER™ device to improve PHE level testing procedures. We hypothesize that availability of convenient and accurate home PHE monitoring will improve the frequency of PHE monitoring by patients with PKU, and that this will lead to better PHE control. The expected outcomes include a significant reduction in PHE levels, better real-time PHE control, and clinical justification for development of a hand-held device in the future. Specific Aim 1 is to clinically validate the FINDERTM PHE assay by comparing PHE results obtained on the device to results from the standard clinical laboratory assay. We will use discarded whole blood samples from patients in the PKU clinic at the Children’s Hospital of Pittsburgh spanning the clinically relevant range of 60 to 1,200 mol/L. We hypothesize that the levels obtained with the FINDERTM will be equivalent to those measured clinically using standard technologies. Specific Aim 2 is to test the design of our microfluidics device in the home setting. Specific Aim 2a is to provide hands-on training of the FINDER™ device in a controlled clinic setting. Specific Aim 2b is to convene focus groups to optimize the in-home user interface and evaluate training materials. Specific Aim 3 is to demonstrate that frequent PHE monitoring at home will be more effective in reducing patient PHE levels than a similar regimen of frequent contact without concurrent measurement of PHE levels. Thus, this project will establish not only the technical capabilities of our PHE monitoring system, but also the efficacy of incorporating the system into routine care in chronic PKU disease management.