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Key sources

The following summarized guidelines for the evaluation and management of phenylketonuria are prepared by our editorial team based on guidelines from the American College of Obstetricians and Gynecologists (ACOG 2020), the European Society for Phenylketonuria and Allied Disorders (ESPKU 2017), the Genetic Metabolic Dietitians International (GMDI/SERC 2016), the American College of Medical Genetics (ACMG 2014), and the U.S. Preventive Services ...
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Screening and diagnosis

Screening in newborns
As per ACMG 2014 guidelines:
Obtain screening for phenylalanine hydroxylase deficiency in newborns by tandem mass spectrometry.
Recognize that a prenatal diagnosis of phenylalanine hydroxylase deficiency can only be established using DNA-based methods.
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Diagnostic investigations

Blood amino acid analysis: as per ACMG 2014 guidelines, obtain quantitative blood amino acid measurement in newborns with positive screening results.

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  • Pterin analysis

  • Genetic testing

  • Mental health assessment

Medical management

Indications for treatment: as per ESPKU 2017 guidelines, consider classifying patients with phenylalanine hydroxylase deficiency as either not requiring treatment or requiring diet or tetrahydrobiopterin, or both, to maintain blood phenylalanine concentrations in the recommended range.
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  • Treatment targets

  • Tetrahydrobiopterin

  • Combination therapy

Nonpharmacologic interventions

Protein and phenylalanine intake: as per GMDI/SERC 2016 guidelines, adjust intact protein intake to meet the patient's recommended phenylalanine intake (for anabolism and maintaining an appropriate blood phenylalanine concentration).
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  • Breast milk

  • Medical foods

  • Tyrosine supplementation

  • Large neutral amino acid supplementation

Specific circumstances

Pregnant patients, pre-pregnancy counseling: as per ACOG 2020 guidelines, provide pre-pregnancy consultation with a maternal-fetal medicine specialist and genetic counseling, as well as ensure co-management with a metabolic geneticist or specialist involved in the patient's care, in all reproductive-aged patients with phenylalanine hydroxylase deficiency. Provide information on reproductive options and family planning as well as management of maternal phenylalanine hydroxylase deficiency before, during, and after pregnancy.

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  • Pregnant patients (fetal assessment)

  • Pregnant patients (treatment targets)

  • Pregnant patients (diet)

  • Pregnant patients (large neutral amino acids)

  • Pregnant patients (tetrahydrobiopterin)

  • Pregnant patients (monitoring)

  • Pregnant patients (special circumstances)

  • Pregnant patients (postnatal care)

Patient education

General counseling
As per GMDI/SERC 2016 guidelines:
Encourage all patients to follow treatment recommendations throughout their lives, including patients who have relaxed their diet restrictions and patients who have never been treated. Recognize and address individual barriers impeding success.
Adopt clinic procedures enhancing adherence to the nutritional recommendations of "diet for life" by providing individualized educational strategies, referrals to appropriate social service and mental health professionals, age-appropriate group activities, and a plan for the transition from pediatric to adult clinical services.

Follow-up and surveillance

Clinical and laboratory follow-up: as per ESPKU 2017 guidelines, obtain lifelong, systematic follow-up in specialized metabolic centers in all adult patients with phenylketonuria because of specific risks that might occur during adulthood.
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