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Table 2 Minimum requirements for the management and follow-up of patients with PKU

From: The complete European guidelines on phenylketonuria: diagnosis and treatment

  Childhood (<12 y) Adolescence (12–18 y) Adulthood (≥18 y) excluding maternal PKU Maternal PKU
Outpatient visit Given good clinical and metabolic control:
Age 0–1 years: every 2 months
Age 1–12 years: twice per year
Extra clinic visit as indicated
Given good clinical and metabolic control:
twice per year
Extra clinic visit as indicated
Given good clinical and metabolic control:
once per year
Extra clinic visit as indicated
Given good clinical and metabolic control: once per trimester
Extra clinic visit as indicated
Clinical nutritional assessment Every outpatient visit: dietary assessment (3-day food record/24 h recall), anthropometric parameters (weight, height, BMI) and clinical features of micronutrient and Phe deficiency (especially anorexia, listlessness, alopecia, perineal rash) Every outpatient visit: dietary assessment (3-day food record/24 h recall), anthropometric parameters (weight, height, BMI) and clinical features of micronutrient and Phe deficiency Every 12–24 months: dietary assessment (3-day food record/24 h recall), anthropometric parameters (weight, height, BMI) and clinical features of micronutrient and Phe deficiency Every outpatient visit:dietary assessment (3-day food record/24 h recall) and weight
Metabolic control Age 0–1 year weekly Phe
Age 1–12 years fortnightly Phe
Increased frequency as indicated
Annually: plasma amino acids
Monthly Phe
Increased frequency as indicated
Annually: plasma amino acids
Monthly Phe
Increased frequency as indicated
Annually: plasma amino acids
Pre-conceptionally: weekly
Pregnancy: twice weekly
Increased frequency as indicated
Pre-conceptionally: plasma amino acids
Biochemical nutritional assessment Annual measurement of plasma homocysteine and/or methylmalonic acid, haemoglobin, MCV and ferritin. All other micronutrients (vitamins and minerals including calcium, zinc, selenium) or hormones (parathyroid hormone) if clinically indicated Pre-conception and at the start of pregnancy:
folic acid, vitamin B12, plasma homocysteine and/or methylmalonic acid, ferritin, full blood count
Pregnancy: when indicated
Bone Density BMD measurement only indicated when there are specific clinical reasons or when patients are known to be at particular risk of metabolic bone disease The first measurement of BMD should be undertaken during late adolescence
- When BMD is abnormal, DXA (with or without change of treatment) should be repeated after 1 year. If osteoporosis (BMD < -2.5 SD) persists despite optimization of diet and physical activity, other possible causes of osteoporosis should be investigated. Treatment (including consideration of bisphosphonates) should be determined by osteoporosis severity.
-  If BMD results are still low but stable, yearly measurement is unnecessary. - When BMD is normal, no repeat measurement is necessary. Further study need only be considered when there are clinical reasons to do so.
BMD measurement is only indicated when there are specific clinical reasons or when patients are known to be at particular risk of metabolic bone disease Not indicated
Neurocognitive functions Only neurocognitive tests when indicated. Testing at age 12 years
Proposed domains of neurocognitive testing:
IQ, perception/visuospatial functioning, EF (divided into inhibitory control, working memory and cognitive flexibility) and motor control.
Extra neurocognitive tests as indicated.
Testing at age 18 years
Proposed domains of neurocognitive testing:
IQ, perception/visuospatial functioning, EF (divided into inhibitory control, working memory and cognitive flexibility) and motor control.
Extra neurocognitive tests as indicated.
Not indicated
Adaptive issues (e.g. clinical relevant behavioural problems) Annually: clinical assessment/discussion Annually: clinical assessment/discussion
Screening at age 12 years
Annually: clinical assessment/discussion
Screening at age 18 years
Not indicated
Neurological complications If neurodegeneration occurs If neurodegeneration occurs Annually: clinical examination Not indicated
Psychosocial functioning and wellbeing and QOL Annually: Clinical assessment/discussion
Once during childhood: (PKU-)QOL questionnaire
Annually: Clinical assessment/discussion
Once during adolescence: (PKU-)QOL questionnaire
Annually: Clinical assessment/discussion
Once during adulthood: (PKU-)QOL questionnaire
Especially in case of not becoming pregnant, the patient may need support
Psychiatric examination At onset of symptoms of psychiatric disturbances At onset of symptoms of psychiatric disturbances At onset of symptoms of psychiatric disturbances Not indicated
White matter abnormalities (MRI) When there is an unexpected clinical course and/or unexpected neurological deficits When there is an unexpected clinical course and/or unexpected neurological deficits When there is an unexpected clinical course and/or unexpected neurological deficits Not indicated
Age group specific investigations / / / Ultrasound at 18–22 weeks of pregnancy with screening for organ development (especially if there is lack of optimal metabolic control)
     Echocardiogram in all infants who are conceived by women with either high blood Phe levels or poor maternal blood Phe control during pregnancy