Abstract
Tyrosinemia type I (HTI) is treated with nitisinone, a tyrosine (Tyr) and phenylalanine (Phe)-restricted diet, and supplemented with a Tyr/Phe-free protein substitute (PS). Casein glycomacropeptide (CGMP), a bioactive peptide, is an alternative protein source to traditional amino acids (L-AA). CGMP contains residual Tyr and Phe and requires supplementation with tryptophan, histidine, methionine, leucine, cysteine and arginine. Aims: a 2-part study assessed: (1) the tolerance and acceptability of a low Tyr/Phe CGMP-based PS over 28 days, and (2) its long-term impact on metabolic control and growth over 12 months. Methods: 11 children with HTI were recruited and given a low Tyr/Phe CGMP to supply all or part of their PS intake. At enrolment, weeks 1 and 4, caregivers completed a questionnaire on gastrointestinal symptoms, acceptability and ease of PS use. In study part 1, blood Tyr and Phe were assessed weekly; in part 2, weekly to fortnightly. In parts 1 and 2, weight and height were assessed at the study start and end. Results: Nine of eleven children (82%), median age 15 years (range 8.6–17.7), took low Tyr/Phe CGMP PS over 28 days; it was continued for 12 months in n = 5 children. It was well accepted by 67% (n = 6/9), tolerated by 100% (n = 9/9) and improved gastrointestinal symptoms in 2 children. The median daily dose of protein equivalent from protein substitute was 60 g/day (range 45–60 g) with a median of 20 g/day (range 15 to 30 g) from natural protein. In part 2 (n = 5), a trend for improved blood Tyr was observed: 12 months pre-study, median Tyr was 490 μmol/L (range 200–600) and Phe 50 μmol/L (range 30–100); in the 12 months taking low Tyr/Phe CGMP PS, median Tyr was 430 μmol/L (range 270–940) and Phe 40 μmol/L (range 20–70). Normal height, weight and BMI z scores were maintained over 12 months. Conclusions: In HTI children, CGMP was well tolerated, with no deterioration in metabolic control or growth when studied over 12 months. The efficacy of CGMP in HTI needs further investigation to evaluate the longer-term impact on blood Phe concentrations and its potential influence on gut microflora
Highlights
IntroductionHereditary Tyrosinemia Type I (HTI), a rare inherited metabolic disorder of tyrosine metabolism, causes abnormal production of toxic metabolites (fumarylacetoacetate, maleylacetoacetate, succinylacetoacetate and succinylacetone), responsible for liver cirrhosis, renal tubular disease and vitamin D resistant rickets [1,2]
Hereditary Tyrosinemia Type I (HTI), a rare inherited metabolic disorder of tyrosine metabolism, causes abnormal production of toxic metabolites, responsible for liver cirrhosis, renal tubular disease and vitamin D resistant rickets [1,2]
To reduce blood tyrosine to an accepted treatment range of 200 to 400 μmol/L [3], a lifelong phenylalanine/tyrosine-restricted diet supplemented with a phenylalanine/tyrosine-free protein substitute is recommended
Summary
Hereditary Tyrosinemia Type I (HTI), a rare inherited metabolic disorder of tyrosine metabolism, causes abnormal production of toxic metabolites (fumarylacetoacetate, maleylacetoacetate, succinylacetoacetate and succinylacetone), responsible for liver cirrhosis, renal tubular disease and vitamin D resistant rickets [1,2]. There are no publications studying the outcome of patients with HTI when given CGMP as a protein substitute This two-part prospective interventional study aimed to investigate the acceptability, growth and metabolic control in a group of children with HTI given low Tyr/Phe CGMP (study product) as part of their protein intake over 12 months. This was a 2-part prospective intervention study (Figure 1). Protein Substitutes Used in the Study The study product (Tyr sphere, a test product from Vitaflo International Ltd., Liverpool, UK) was a berry-flavored powder containing 11 mg of tyrosine and 36 mg of phenylalanine for each 20 g protein equivalent It was reconstituted by adding 120 mL of water. Natural Protein Intake All the children were prescribed a tyrosine/phenylalanine-restricted diet and the estimated median prescribed natural protein intake was 20 g/day (range 15 to 30 g)
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