Factors affecting metabolism and metabolic control in phenylketonuria

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.<br/>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 improved<br/>gastrointestinal symptoms, it had a negative impact on blood phenylalanine control when providing 100% of the protein equivalent requirements from protein substitute.<br/>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.

Author dc:creator

• Amorim Pinto, Alex

Contributors dc:contributor

• Anita MacDonald, Júlio César Rocha, Anne Payne, Mary Hickson

• Phenylketonuria
• Phenylalanine
• Metabolic control

Language dc:language

eng

Repository record dc:identifier

https://pearl.plymouth.ac.uk/hp-theses/29

OAI identifier oai:identifier

oai:pearl.plymouth.ac.uk:hp-theses-1031