Limitation of dietary PHE and supplementation of 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 health maintenance. Newer adjunctive therapies are appropriate for some individuals but require continued nutrition intervention and monitoring.

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 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 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 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). The safety of use during pregnancy and lactation in women with PKU is still being studied. 

While large neutral amino acids, used as an adjuvant therapy, have allowed improvement in psychosocial characteristics in some individuals with PKU, they do not result in blood PHE in the target range.

Implementing the recommendations would:

• Reduce variations in clinical practice and services across medical centers
• Guide practice decisions that integrate medical and nutrition management/therapy
• Provide clinicians with criteria to make recommendations for nutrition management or recommend adjuvant therapies
• Design quality nutrition care based on individual metabolic and/or genetic alteration
• Improve clinical outcomes and clinician effectiveness
• Enhance quality of life, prevent untoward consequences and complications, and reduce associated medical, educational and social costs