The clinician should monitor plasma phenylalanine in the PKU patient, child or adult throughout life.

In the child with PKU normal development and adequate psychosocial integration will only be achieved if the phenylalanine value is maintained within the following limits:

• child under 10 years 120-360 micromoles/L (39,40,41);
• adolescent 120-600 micromoles/L (39);
• child over 16 years and adult 450-1,200 micromoles/L

Plasma phenylalanine monitoring will be performed according to age as follows:

• infant up to 1 year....................……..monthly;
• child 1 to 3 years...............................monthly;
• child 4 - 9 years ...........................….quarterly;
• child 10 - 15 years .....................…...monthly;
• adult ......................................………monthly.

Phenylalanine monitoring allows identification of phenylalanine safety limits being exceeded (phenylalanine excess/deficiency). Phenylalanine tolerance is an indicator of dietary adaptation.

When plasma phenylalanine concentrations are found to exceed the safe range, the return of phenylalanine to the safe range is achieved by gradually adjusting the diet in the desired direction with small changes to avoid large variations in Phe values. Increased phenylalanine levels are most commonly caused by dietary excess of phenylalanine (dietary misunderstanding, dietary non-compliance, over-prescription of phenylalanine in diets).

Other causes can be infections, trauma, insufficient protein and/or energy intake. A fall in plasma phenylalanine concentration below the safe range may be caused by insufficient prescription of dietary protein and phenylalanine, misunderstanding of dietary composition, inappetence.

Low values below 25-30 myocromoli/L can lead to decreased appetite, decreased rate of statural growth and increased plasma phenylalanine concentration through muscle protein degradation. Prolonged phenylalanine deficiency can lead to mental retardation, growth arrest, osteopenia anaemia.

The physician should clinically monitor the PKU patient regardless of age.

During the clinical examination the doctor will assess diet, physical activity, weight, head circumference in children, height, BMI, neuropsychological development (in children), psychosocial integration. Dietary monitoring is carried out for 3 days followed by calculation of energy, amino acid, carbohydrate, lipid intake. Dietary monitoring is also of particular value when the patient is treated with Sapropterin.

If the dietary investigation shows a suboptimal dietary intake of amino acids the doctor will recommend supplementing the investigations by dosing amino acids, vitamins (vitamins vitamin A, C, E coenzyme Q 10, vitamin B 2, B 6, B 12, and folate, vitamin D) micronutrients, (calcium, phosphorus, selenium, zinc), ferritin, albumin HDL/LDL-cholesterol, homocysteine, fatty acids, methylmalonic acid.

The clinician will also order investigations to check for bone mineralisation in adolescents. If phenylalanine is within normal limits no further investigations are necessary.

Clinical monitoring will be performed at the following frequency:

• infant - 3 years ......................................................... every 3 months;
• child 4 - 9 years ........................................................ every 6 months;
• child 10 -15 years ..................................................... at 6 months;
• adult ................................................................…….. every 6 months.

In patients on Sapropterin treatment the physician will recommend a monthly assessment of phenylalanine tolerance based on the determination of plasma Phe concentration under conditions of progressive dietary relaxation achieved by increasing dietary intake of natural protein.

Sapropterin treatment leads to increased phenylalanine tolerance which allows an increase in dietary intake of natural protein up to 2-3 times the initial level. As a result of treatment the diet is relaxed or even eliminated, significantly improving the quality of life of patients.

Assessment and monitoring of the patient with phenylketonuria should be carried out by an interdisciplinary team consisting of paediatrician, neonatologist, nutritionist, neuropsychiatrist, psychologist, dietician. The diagnostic, developmental and therapeutic complexity of phenylketonuria requires the collaboration of medical staff from different specialties, each contributing to the personalised management of the affected person.