Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach

https://doi.org/10.1016/j.ymgme.2015.03.006Get rights and content

Highlights

  • In PKU, the total protein prescribed varied widely between European centres.

  • The amount of total protein appears to be influenced by geographical European region.

  • North Europe prescribed highest amounts of total protein and least in West Europe.

  • All PKU centres give in excess of the FAO/WHO/UNU safe levels of protein intake.

Abstract

Background

There appears little consensus concerning protein requirements in phenylketonuria (PKU).

Methods

A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics.

Results

The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants < 1 year, > 2–3 g/kg/day; 1–3 years of age, > 2–3 g/kg/day; 4–10 years of age, > 1.5–2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants < 1 year, 2.5 g/kg/day, 1–3 years of age, 2 g/kg/day; 4–10 years of age, 1.5–2 g/kg/day), than by Eastern Europe (n = 4 centres) (infants < 1 year, 2.5 g/kg/day, 1–3 years of age, > 2–2.5 g/kg/day; 4–10 years of age, > 1.5–2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants < 1 year, > 2–2.5 g/kg/day, 1–3 years of age, 1.5–2 g/kg/day; 4–10 years of age, 1–1.5 g/kg/day). Total protein prescription was similar in patients aged > 10 years (1–1.5 g/kg/day) and maternal patients (1–1.5 g/kg/day).

Conclusions

The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Introduction

Phenylalanine-free protein substitute is a primary source of protein in patients with PKU treated by a low phenylalanine diet only. This is predominantly based on phenylalanine-free l-amino acids. It is essential to prevent protein deficiency, optimize metabolic control [1], [2], [3], [4], and it may block phenylalanine transport across the blood brain barrier [5], [6]. Phenylalanine-free protein substitute is likely to supply 52 to 80% of the total protein intake [7], [8], [9], but there is no robust evidence base to support the optimal dose due to a lack of studies examining its utility. Nevertheless, developing universal guidelines on protein substitute dosage that are supported and agreed by health professionals are necessary to provide consistent, effective and cost efficient care to patients. However, there is little harmony between professionals on optimal amounts.

There have been 2 different approaches to prescribing the dose of protein substitute.

  • 1.

    Some PKU centres recommend a higher dose of protein equivalent than the FAO/WHO/UNU [10] safe levels of protein intake [11]. This may lead to an increase in nitrogen retention, prevention of protein insufficiency [12], improved phenylalanine tolerance [11], [13], [14], contribute to better phenylalanine control [1], as well as provide a higher intake of large neutral amino acids [15]. There is also evidence that l-amino acids may be poorly utilised and are less efficacious than the low phenylalanine-peptide based glycomacropeptide (GMP) both in subjects with PKU [16] and PKU mice [17], [18]. Compared with a casein rich protein [19], there is suggestion of less efficient transfer of amino acids into tissue and plasma proteins with l-amino acid supplements [20], [21].

  • 2.

    Some centres advocate the same dose of protein equivalent (from a combined intake of phenylalanine-free protein substitute and natural/intact protein) as for the healthy population [22], [23]. Protein substitute is expensive and adherence maybe suboptimal. Adults with PKU (excluding pregnancy) do not have higher protein requirements when the majority of dietary protein is provided by amino acids [24]. Also long term intake of phenylalanine-free l-amino acids has been linked to proteinuria and decreased GFR [9] but further study is required.

It is possible that by examining the current European prescribing trends it may help unravel health professional attitudes and decision making processes on protein substitute dosing. Therefore, an internet questionnaire on dietary practices with protein substitute prescription (dosage, type, and administration) was sent to dietitians and physicians who were members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG).

Section snippets

Materials and methods

A cross-sectional computer questionnaire was distributed to all European dietitian members of the Society for the Study of Inborn Errors of Metabolism (SSIEM-DG). SSIEM-DG members then cascaded the questionnaire to dietitians and/or physicians within their own country between July and December 2013. The questionnaire consisted of 26 multiple choice and short answer questions. The following data were collected by age group: total protein intake prescribed (sourced from natural/intact protein and

Results

Sixty three questionnaires were completed by dietitians/physicians from PKU centres from 18 countries. The countries were (n = centre number): Austria (n = 1); Belgium (n = 7); Denmark (n = 1); France (n = 2); Germany (n = 6); Hungary (n = 1); Ireland (n = 1); Italy (n = 2); Netherlands (n = 7); Norway (n = 1); Poland (n = 2); Portugal (n = 4); Spain (n = 2); Sweden (n = 5); Switzerland (n = 2); Turkey (n = 2); United Kingdom (n = 16); and Russia (n = 1). The countries were then divided into 4 European regions: Eastern, Western,

Discussion

In PKU, l-amino acid supplements remain the most extensive protein substitute used by European countries with GMP still not widely available in Europe. In children ≤ 10 years of age the amounts of total protein prescribed for each age category were variable and strongly influenced by European location. Overall most Western European PKU centres prescribed less total protein than other regions in Europe. In children under 1 year of age, Swiss centres prescribed a total protein intake of less than 2 

Conflicts of interest

Kirsten Ahring — a member of the European Nutrition Expert Panel (Merck Serono International).

Amaya Bélanger-Quintana — received honoraria for speaking or funding for conferences from Nutricia and Mead-Johnson. A member of the European Nutrition Expert Panel (Merck Serono International), the Sapropterin Advisory Board (Merck Serono International), and the KAMPER Advisory Board (Merck Serono International).

Alberto Burlina — received honoraria from Nutricia and Merck Serono, a member of the

Authors' contributions

All authors were involved in data collection, interpretation of data, critical revision of the paper for important intellectual content and final approval of the version to be published. FJV and AM were additionally involved in the initial conception and design and AM and SE in the collation of data and drafting of the initial article. AM will serve as a guarantor for the article.

Acknowledgments

Source of funding: there has been no formal funding for this study.

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