Abstract

Phenylketonuria (PKU) is an inherited metabolic disorder treated by a phenylalanine restricted diet in order to avoid neurocognitive impairment. Blood phenylalanine is the main outcome marker which is modulated by many dietary factors. Traditionally, L-amino acid-based protein substitutes are the main nitrogen source but more recently glycomacropeptide-based protein substitutes (GMP) have been introduced and are associated with several health benefits. The following aspects were studied in this thesis: 1) metabolic control achieved in patients with PKU compared with the European PKU guidelines; 2) life-long change in natural protein tolerance; 3) impact on metabolic control of different natural protein sources (animal vs. plant); 4) effect of unmeasured amounts of fruit and vegetables containing phenylalanine 76-100mg/100g on metabolic control; and 5) health benefits of GMP.The results of these studies showed that blood phenylalanine increased with age especially in patients with classical PKU (cPKU) and a higher frequency of blood phenylalanine monitoring was associated with better metabolic control. Natural protein (NP) intake was at its highest in patients aged 19-30y and patients with cPKU tolerated less than 50% of NP compared with patients with mild PKU (mPKU). Over restriction of NP was observed in mPKU patients. Sixty five percent (n=26/40) were able to increase NP by a median of 12g/day without loss of metabolic control. Animal protein sources had a higher impact on blood phenylalanine control compared with plant sources. However, some patients were unable to tolerate fruit and vegetables containing phenylalanine 76-100 mg/100g when given in uncontrolled amounts. Furthermore, exchange-free foods in the current dietary system added an extra 40% NP to the prescribed amount without any negative impact on blood phenylalanine control. Although GMP improvedgastrointestinal symptoms, it had a negative impact on blood phenylalanine control when providing 100% of the protein equivalent requirements from protein substitute.Overall, this research program described novel data that will impact future PKU guidelines and will help influence and improve the daily care of patients with PKU.

Keywords

Phenylketonuria, Phenylalanine, Metabolic control

Document Type

Thesis

Publication Date

2025

Embargo Period

2025-06-16

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