Limitation of dietary PHE and supplementation with medical food (containing TYR) is an effective treatment for PKU. However, the diet is restrictive and long-term adherence is difficult, often leading to suboptimal control in older children and adults. High blood PHE concentrations are associated with neuropsychiatric disorders and executive functioning defects. Outcome is therefore dependent not only on early diagnosis with initiation of treatment; but also on consistent treatment and monitoring to maintain appropriate PHE concentrations, growth and optimal health maintenance. Newer adjunctive and alternate therapies are appropriate for some individuals but require continued management and monitoring of nutritional status.
This guideline recommends that individuals with PKU maintain blood PHE between 120-360 μmol/L through their lifetime. Unnecessary treatment, or more stringent treatment than needed for optimal outcomes, has the potential to create psychosocial and nutritional costs for individuals with PKU. Such treatment may be burdensome and stigmatizing (F.2525), may have nutritional consequences (vitamin/mineral/protein deficiencies) (L.160), and may increase health care costs, especially since access to medical foods and care is difficult for many (F.2629). Many older children and adults currently do not adhere well even to more liberal blood PHE recommendations (F.1346, F.1297), so may be unlikely to attain more strict blood PHE recommendations.
Individuals who do not adhere to all aspects of therapy, whether dietary or pharmacotherapy, are also at risk for the consequences of elevated blood PHE and possible nutritional deficiencies.
Side effects of sapropterin, used as an adjuvant therapy, include gastrointestinal distress (especially if the drug is not consumed with food) and headaches (F.2629).
While large neutral amino acids have allowed improvement in psychosocial characteristics in some individuals with PKU, they do not result in blood PHE in the target range.
Pegvaliase, an enzyme substitute for the PAH enzyme, can cause adverse events, especially those related to immune response to the pegylated medication. REM procedures are in place to monitor adverse reactions and treat with appropriate medical attention. Pegvaliase use can result in hypophenylalaninemia and recomendations within the guideline address this (F.4459). The safety of use of pegvaliase during pregnancy and lactation in women, and in children with PKU is still being studied.
Implementing the recommendations would: