Strategies to engage lost to follow-up patients with phenylketonuria in the United States: Best practice recommendations

Background: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by mutations in the gene encoding phenylalanine hydroxylase, an enzyme that converts phenylalanine to tyrosine. Untreated, PKU is characterized by a range of neuropsychological and neurocognitive impairments. Due to ubiquitous newborn genetic screening programs, treatment for PKU can be commenced shortly after birth and can prevent many of the severe manifestations of the disease. However, lifelong management is critical for patients with PKU as high levels of phenylalanine are neurotoxic. As for all chronic diseases, long-term management can be challenging and most adult patients with PKU become lost to follow-up (LTFU). A survey of PKU clinics across the United States and a multidisciplinary Expert Meeting were conducted to develop best practices to engage LTFU patients with PKU. Results: We defined LTFU patients with PKU as patients with no contact with the clinic for at least 2 consecutive years. Combining the results from our survey and our discussion at the Expert Meeting, we have prepared six best practice recommendations to engage LTFU patients with PKU: 1) Ensure patients are aware of the current treatment guidelines for PKU; 2) Communicate to patients any new treatment and diet options as they become available for PKU; 3) Consider the neuropsychological and neurocognitive aspects of PKU; 4) Prioritize motivated LTFU patients; 5) Explore new approaches of outreach to LTFU patients; and 6) Formalize approaches to track and/or identify PKU patients. Conclusion: We strongly advocate the importance of engaging LTFU patients with PKU and encourage implementation of our best practice recommendations. Although it takes time and effort to engage LTFU patients, we believe that clinics are capable of supporting this significant patient group.