Search Results (7)

Amino acid (AA)-related inherited metabolic disorders (IMDs) and urea cycle disorders (UCDs) require strict dietary management including foods low in protein such as fruits, vegetables and starchy roots. Despite this recommendation, there are limited data on the AA content of many of these foods. The aim of this study is to describe an analysis of the protein and AA content of a range of fruits, vegetables and starchy roots, specifically focusing on amino acids (AAs) relevant to AA-related IMDs such as phenylalanine (Phe), methionine (Met), leucine (Leu), lysine (Lys) and tyrosine (Tyr). AA analysis was performed using high-performance liquid chromatography (HPLC) on 165 food samples. Protein analysis was also carried out using the Dumas method. Foods were classified as either ‘Fruits’, ‘Dried fruits’, ‘Cruciferous vegetables’, ‘Legumes’, ‘Other vegetables’ or ‘Starchy roots’. ‘Dried fruits’ and ‘Legumes’ had the highest median values of protein, while ‘Fruits’ and ‘Cruciferous vegetables’ contained the lowest median results. ‘Legumes’ contained the highest and ‘Fruits’ had the lowest median values for all five AAs. Variations were seen in AA content for individual foods. The results presented in this study provide useful data on the protein and AA content of fruits, vegetables and starchy roots which can be used in clinical practice. This further expansion of the current literature will help to improve diet quality and metabolic control among individuals with AA-related IMDs and UCDs. Full article

In the UK, different dietary systems are used to calculate protein or tyrosine/phenylalanine intake in the dietary management of hereditary tyrosinaemia, HTI, II and III (HT), with no systematic evidence comparing the merits and inadequacies of each. This study aimed to examine the current UK dietary practices in all HTs and, using Delphi methodology, to reach consensus agreement about the best dietary management system. Over 12 months, five meetings were held with UK paediatric and adult dietitians working in inherited metabolic disorders (IMDs) managing HTs. Eleven statements on the dietary system for calculating protein or tyrosine/phenylalanine intake were discussed. Dietitians from 12 of 14 IMD centres caring for HT patients participated, and 7/11 statements were agreed with one Delphi round. Nine centres (three abstentions) supported a 1 g protein exchange system for all foods except fruit and vegetables. The same definitions used in the UK for phenylketonuria (PKU) were adopted to define when to calculate foods as part of a protein exchange system or permit them without measurement. Fruit and vegetables contain a lower amount of tyrosine/phenylalanine per 1 g of protein than animal and cereal foods. The correlation of tyrosine vs. phenylalanine (mg/100 g) for vegetables and fruits was high (r = 0.9). In Delphi round 2, agreement was reached to use the tyrosine/phenylalanine analyses of fruits/vegetables, for their allocation within the HT diet. This allowed larger portion sizes of measured fruits and vegetables and increased the variety of fruit and vegetables that could be eaten without measurement. In HTs, a combined dietary management system will be used: 1 g protein exchanges for cereal and milk protein sources and tyrosine/phenylalanine exchanges for fruit and vegetables. Intensive, systematic communication with IMD dietitians and reappraisal of the evidence has redefined and harmonised HT dietary practice across the UK. Full article

This review briefly discusses the discovery of the mode of action of the triketone herbicide, 2-(2-nitro-4-trifluormethylbenzoyl)-1,3-cyclohexanedione and its use as a drug Nitisinone for the treatment of inborn errors of tyrosine metabolism. Nitisinone is a potent reversible tight-binding inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, involved in the catabolism of the amino acid tyrosine. Nitisinone is used to treat the rare disease hereditary tyrosinaemia type 1 where the last enzyme in the breakdown of tyrosine, fumarylacetoacetase is deficient. Nitisinone is also used to treat patients with alkaptonuria where the enzyme homogentisic acid oxidase is deficient. Articles in this issue discuss metabolites of tyrosine catabolism in healthy patients and those with alkaptonuria. Full article

In a retrospective review, we aimed to assess long-term growth in 17 patients (n = 11 males) with hereditary tyrosinaemia type I (HTI). Median age at assessment was 15.6 years (5.7–26.6 years) and median age at diagnosis was 1 month (range: 0–16 months), with 35% (n = 6/17) symptomatic on presentation. From the age of 8 years, there was a noticeable change in median height, weight, and body-mass-index [BMI]-z-scores. Median height-for-age z-scores were consistently ≤ −1 (IQR −1.6, −0.5) during the first 8 years of life but increased with age. Weight-for-age z-scores ranged between −1 to 0 (IQR −1.2, 0.1) in the first 8 years; then increased to > 0.5 (IQR −0.3, 1.3) by age 16 years, and BMI-for-age z-scores ranged from 0 to 1 (IQR −0.7, 1.3) up to 8 years, and >1 (IQR −0.2, 1.9) until 16 years. The percentage of overweight and obesity was lowest in children aged < 5 years, and consistently > 40% in patients aged between 7 to 16 years. The prescribed total protein intake was associated with improved height growth (p < 0.01). Impaired growth in early life improved with age achieving normal population standards. Further studies are needed to investigate factors that influence growth outcome in HTI patients. Full article

Background: Tyrosinaemia type 1 is a rare inherited metabolic disease caused by an enzyme defect in the tyrosine degradation pathway. It is treated using nitisinone and a low-protein diet. In a workshop in 2013, a group of nutritional specialists from Germany, Switzerland and Austria agreed to advocate a simplified low-protein diet and to allow more natural protein intake in patients with tyrosinaemia type 1. This retrospective study evaluates the recommendations made at different treatment centers and their impact on clinical symptoms and metabolic control. Methods: For this multicenter study, questionnaires were sent to nine participating treatment centers to collect data on the general therapeutic approach and data of 47 individual patients treated by those centers. Results: Dietary simplification allocating food to 3 categories led to increased tyrosine and phenylalanine blood concentrations without weighing food. Phenylalanine levels were significantly higher in comparison to a strict dietary regimen whereas tyrosine levels in plasma did not change. Non-inferiority was shown for the simplification and liberalization of the diet. Compliance with dietary recommendations was higher using the simplified diet in comparison to the stricter approach. Age correlates negatively with compliance. Conclusions: Simplification of the diet with increased natural protein intake based on three categories of food may be implemented in the diet of patients with tyrosinaemia type 1 without significantly altering metabolic control. Patient compliance is strongly influencing tyrosine blood concentrations. A subsequent prospective study with a larger sample size is necessary to get a better insight into the effect of dietary recommendations on metabolic control. Full article

In a longitudinal retrospective study, we aimed to assess natural protein (NP) tolerance and metabolic control in a cohort of 20 Hereditary Tyrosinaemia type I (HTI) patients. Their median age was 12 years ([3.2–17.7 years], n = 11 female, n = 8 Caucasian, n = 8 Asian origin, n = 2 Arabic and n = 2 Indian). All were on nitisinone (NTBC) with a median dose of 0.7 g/kg/day (range 0.4–1.5 g/kg/day) and were prescribed a tyrosine (Tyr)/phenylalanine (Phe)-restricted diet supplemented with Tyr/Phe-free L-amino acids. Data were collected on clinical signs at presentation, medical history, annual dietary prescriptions, and blood Phe and Tyr levels from diagnosis until transition to the adult service (aged 16–18 years) or liver transplantation (if it preceded transition). The median age of diagnosis was 2 months (range: 0 to 24 months), with n = 1 diagnosed by newborn screening, n = 3 following phenylketonuria (PKU) screening and n = 7 by sibling screening. Five patients were transplanted (median age 6.3 years), and one died due to liver cancer. The median follow-up was 10 years (3–16 years), and daily prescribed NP intake increased from a median of 5 to 24 g/day. Lifetime median blood Tyr (370 µmol/L, range 280–420 µmol/L) and Phe (50 µmol/L, 45–70 µmol/L) were maintained within the target recommended ranges. This cohort of HTI patients were able to increase the daily NP intake with age while maintaining good metabolic control. Extra NP may improve lifelong adherence to the diet. Full article

From 3–4 June, 2016, the 23^rd Annual Meeting of the German Society for Newborn Screening (Deutsche Gesellschaft für Neugeborenenscreening, DGNS) was held at the University Hospital Heidelberg. The meeting was organized by PD Dr. med. Gwendolyn Gramer (conference president) from the Newborn Screening Centreat the University Hospital Heidelberg, Centre for Paediatric and Adolescent Medicine. Prof. Dr. med. Prof. h.c. mult. (RCH) Georg F. Hoffmann, PD Dr. phil. nat. Jürgen G. Okun and PD Dr. med. Gwendolyn Gramer formed the scientific board for the selection of presentations. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. Full article