Monitoring

Blood phenylalanine (phe) levels should be obtained at periodic intervals to monitor the efficacy of therapy in patients with Phenylketonuria (PKU). The recommended minimum interval is:[17]

  • Weekly for infants <1 year of age, whose nutritional requirements change frequently as a result of rapid growth

  • Every 2 weeks from 1 to 12 years of age

  • Monthly after 12 years of age

  • Weekly during preconception

  • Twice weekly during pregnancy

The target therapeutic range for blood phe levels varies across guidelines. In Europe, the European Society of Phenylketonuria and Allied Disorders stratifies recommended targets by age: 120-360 micromol/L (2-6 mg/dL) for individuals under 12 years and 120-600 micromol/L (2-10 mg/dL) for those aged 12 and older.[17]​ In the US, the American College of Medical Genetics and Genomics recommends that all individuals with PKU maintain a mean lifetime phe level of ≤360 micromol/L (≤6 mg/dL).[9]​ Increasing evidence supports stricter recommendations by the US guidelines, as studies have reported that adolescents and young adults with blood phe levels above 240-360 micromol/L (4-6 mg/dL) tend to experience poorer social-cognition and executive functioning, and more severe mental health challenges.[10]​ Levels above or below the therapeutic range should prompt an adjustment in therapy.

A diet diary should be submitted with each blood sample so that the adequacy of the diet can be assessed and adjustments can be made when blood phe levels are not within range. Screening for physical health comorbidities should begin early and continue throughout life, as these comorbidities may occur regardless of age and are influenced by blood phe control.[10] In addition to physical examinations, assessments should include anthropometric measurements, nutritional intake reviews, lipid panels, allergy history (e.g., eczema and rhinitis), and micronutrient levels, such as vitamins B12, D, folate, and zinc.[10] A DEXA scan for bone density should be performed initially by age 12, with follow-up scans as dictated by findings.[10] Vitamin D levels should be monitored regularly, and supplementation should be provided for any deficiencies. If osteopenia is identified, serum calcium, phosphorus, and parathyroid hormone levels should also be obtained. Neuropsychological assessment is recommended if cognitive or behavioural issues are suspected.[17]​ 

The recommended minimum frequency of outpatient visits for patients with good clinical and metabolic control is:[17]

  • Every 2 months for infants aged <1 year

  • Every 6 months from aged 1-18 years

  • Yearly after aged 12 years

  • Once per trimester during pregnancy

Pregnant women with PKU should be monitored closely by physicians familiar with the condition, with ongoing follow-up from a metabolic geneticist and high-risk pregnancy consultants. Additionally, fetal growth assessments and a detailed anatomical survey are recommended to detect potential anomalies or growth restrictions, and fetal echocardiography should be performed to screen for congenital heart defects.[18]

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