Phenylketonuria (PKU) and Tyrosinaemia (TYR) are rare inherited metabolic disorders of amino acid metabolism requiring dietary management. PKU is characterised by an inability to metabolise the essential dietary amino acid phenylalanine (Phe) into tyrosine (Tyr). As such, without appropriate management, PKU can lead to extremely elevated levels of Phe within the blood and brain, which can be detrimental to neurological health. The dietary management of PKU involves restricting dietary sources of Phe. Tyrosinaemia (TYR) is characterised by the inability to metabolise the dietary amino acid Tyr. If left uncontrolled, TYR can lead to serious hepatic, renal and neurological complications. The dietary management of TYR involves restriction of dietary sources of Tyr and Phe (as Phe is converted into Tyr). The dietary management of PKU and TYR involves restricting dietary protein intake to promote optimal metabolic control, whilst meeting all other amino acid and nutrient requirements. As Phe and Tyr are present in significant quantities in nearly all dietary proteins, this usually requires a very low protein diet from food, supplemented with a Phe-free (for PKU) or Phe- and Tyr-free (for TYR) amino acid-based protein substitute. However, compliance with the diet is often poor, with patients commonly going off diet during adolescence and in adulthood. This can lead to entirely preventable, lifelong mental and physiological impairments. Reasons for non-compliance often revolve around the strong taste of amino acid-based protein substitutes, alongside the inability to conform to the normal eating habits of peers.~Three new protein substitutes have been developed to help with compliance in PKU and TYR patients, which are powdered protein substitutes, low in Phe and, low in Phe and Tyr respectively, with a mixed balance of glycomacropeptide (GMP), essential and non-essential amino acids, carbohydrates, fats and micronutrients for the dietary management of PKU and TYR. The protein in GMP-based products for PKU and TYR are based on GMP, a peptide isolated from milk during cheese manufacturing and the only known naturally derived protein source low in Phe and Tyr. The GMP is supplemented with appropriate quantities of other amino acids which are naturally low or not present in GMP, as well as carbohydrates and fats. This differs from traditional formulae which are based wholly on individual, synthetically produced amino acids to provide the source of dietary nitrogen, supplemented with vitamins and minerals. Studies to date have illustrated that PKU patients who replace their regular Phe-free amino acid-based formula with GMP-based foods may have better diet compliance, prefer the taste and may have improved blood Phe control.~This series of case-studies will evaluate the acceptability, compliance, gastrointestinal tolerance and safety of the three GMP-based products for PKU and TYR in 45 patients with PKU and TYR, in both adults and children over 3 years (15 patients per product). The case study will last 29 days in total, including a 1-day baseline period followed by a 28-day intervention period. The case studies will be conducted across multiple specialist metabolic centres in the UK, to meet the UK ACBS and GMS requirements for acceptability studies. A series of case studies is undertaken due to the rarity of these conditions and the difficulty in recruiting these patients to trials.
Three new protein substitutes have been developed to help with compliance in PKU and TYR patients, which are powdered protein substitutes, low in Phe and, low in Phe and Tyr respectively, with a mixed balance of glycomacropeptide (GMP), essential and non-essential amino acids, carbohydrates, fats and micronutrients for the dietary management of PKU and TYR.~This series of case-studies will evaluate the acceptability, compliance, gastrointestinal tolerance and safety of the three GMP-based products for PKU and TYR in 45 patients with PKU and TYR, in both adults and children over 3 years (15 patients per product). The case study will last 29 days in total, including a 1-day baseline period followed by a 28-day intervention period. The case studies will be conducted across multiple specialist metabolic centres in the UK, to meet the UK ACBS and GMS requirements for acceptability studies. A series of case studies is undertaken due to the rarity of these conditions and the difficulty in recruiting these patients to trials.