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 2 a is to provide hands-on training of the FINDER? device in a controlled clinic setting.
Specific Aim 2 b 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.
This project proposes to develop a home devise for PKU patients to test their phenylalanine levels. More frequent monitoring with immediate feedback on test results will allow patients more information to treat their chronic disease and optimize long term intellectual and psychological outcome.