Protein substitutes for phenylketonuria in Europe: access and nutritional composition.

Background/objectives: Protein substitutes (PS) are an essential component in the dietary management of phenylketonuria (PKU). PS are available as phenylalanine-free amino-acid mixtures (AAM), glycomacropeptide-based PS (GMP) and large neutral amino acids (LNAA). There is a lack of information regarding their availability in different countries and comparison of their nutritional composition is limited.

Special low protein foods for phenylketonuria: availability in Europe and an examination of their nutritional profile.

Background: Special low protein foods (SLPF) are essential in the nutritional management of patients with phenylketonuria (PKU). The study objectives were to: 1) identify the number of SLPF available for use in eight European countries and Turkey and 2) analyse the nutritional composition of SLPF available in one of these countries.

Methods: European Nutritionist Expert Panel on PKU (ENEP) members (Portugal, Spain, Belgium, Italy, Germany, Netherlands, UK, Denmark and Turkey) provided data on SPLF available in each country.

Weight Management in Phenylketonuria: What Should Be Monitored.

Background: Severe intellectual disability and growth impairment have been overcome by the success of early and continuous treatment of patients with phenylketonuria (PKU). However, there are some reports of obesity, particularly in women, suggesting that this may be an important comorbidity in PKU. It is becoming evident that in addition to acceptable blood phenylalanine control, metabolic dieticians should regard weight management as part of routine clinical practice.

The challenges of managing coexistent disorders with phenylketonuria: 30 cases.

Introduction: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study.

Methods: Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported.

Development of an in vitro digestive model for studying the peptide profile of breast milk.

Human milk is a highly valuable food for newborns and infants. Its protein fraction plays an important role for the development of the newborn. In the present study, an in vitro digestive model, developed for resembling closely the digestive system of an infant, was applied to human milk in order to identify and characterize the peptide profile.

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

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.

When should social service referral be considered in phenylketonuria?

Lifelong low-phenylalanine (Phe) dietary management is the foundation of care in phenylketonuria (PKU). However, strict monitoring of food intake places a burden on patients and their caregivers, and adherence to the required diet frequently decreases in later childhood and adolescence. Rarely, parents of children with PKU refuse to recognise the importance of treatment and follow-up for this chronic condition.

Overweight and obesity in PKU: The results from 8 centres in Europe and Turkey.

Introduction: In PKU there is little data comparing the prevalence of overweight and obesity in different countries. The aim of this cross sectional study was to evaluate prevalence data from different PKU treatment centres in Europe and Turkey.

Subjects And Methods: In children, body mass index (BMI) and z scores and in adults BMI were calculated in 947 patients (783 children aged < 19 years; 164 adults aged ≥ 19 years) with PKU from centres in Europe and Turkey (Ankara, Birmingham, Brussels, Copenhagen, Groningen, Madrid, Munich and Porto).

Micronutrient status in phenylketonuria.

Patients with phenylketonuria (PKU) encompass an 'at risk' group for micronutrient imbalances. Optimal nutrient status is challenging particularly when a substantial proportion of nutrient intake is from non-natural sources. In PKU patients following dietary treatment, supplementation with micronutrients is a necessity and vitamins and minerals should either be added to supplement phenylalanine-free l-amino acids or given separately.

Main issues in micronutrient supplementation in phenylketonuria.

For almost all patients with PKU, a low phenylalanine diet is the basis of the treatment despite a widely varying natural protein tolerance. A vitamin and mineral supplement is essential and it is commonly added to a phenylalanine-free (phe-free) source of L-amino acids. In PKU, many phe-free L-amino acid supplements have age-specific vitamin and mineral profiles to meet individual requirements.

Use of sapropterin in the management of phenylketonuria: seven case reports.

Sapropterin treatment, with or without dietary treatment, improves blood phenylalanine control, increases phenylalanine tolerance, and may reduce the day-to-day dietary treatment burden in a subset of patients with phenylketonuria (PKU). Balancing the need for maintained control of blood phenylalanine with diet relaxation is complex when administering sapropterin. We present a series of seven patient cases with PKU that illustrate important aspects of using sapropterin with diet in the management of the disorder.

Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers.

Background And Aims: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers.

Methods: Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients.

Results: The mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient.

Optimising growth in phenylketonuria: current state of the clinical evidence base.

Patients with phenylketonuria (PKU) must follow a strict low-phenylalanine (Phe) diet in order to minimise the potentially disabling neuropsychological sequelae of the disorder. Research in this area has unsurprisingly focussed largely on managing blood Phe concentrations to protect the brain. Protein requirements in dietary management of PKU are met mostly from Phe-free protein substitutes with the intake of natural protein restricted to patient tolerance.

Adjusting diet with sapropterin in phenylketonuria: what factors should be considered?

The usual treatment for phenylketonuria (PKU) is a phenylalanine-restricted diet. Following this diet is challenging, and long-term adherence (and hence metabolic control) is commonly poor. Patients with PKU (usually, but not exclusively, with a relatively mild form of the disorder) who are responsive to treatment with pharmacological doses of tetrahydrobiopterin (BH4) have either lower concentrations of blood phenylalanine or improved dietary phenylalanine tolerance.

Blood phenylalanine control in phenylketonuria: a survey of 10 European centres.

Background: Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet.

Objective: A survey was conducted to compare blood Phe control achieved in diet-treated patients with PKU of different age groups in 10 European centres.

Methods: Centres experienced in the management of PKU from Belgium, Denmark, Germany, Italy, The Netherlands, Norway, Poland, Spain, Turkey and the United Kingdom provided retrospective audit data of all patients with PKU treated by diet over a 1-year period.

Long-chain polyunsaturated fatty acids profile in plasma phospholipids of hyperphenylalaninemic children on unrestricted diet.

Introduction: The aim of the present study was to examine whether hyperphenylalaninemic children on unrestricted diet (MHP) may exhibit a different LCPUFA profile from PKU or healthy children in plasma phospholipids.

Patients And Methods: Forty-five MHP children (age 9-14 years) were age and sex matched with 45 PKU and 45 healthy children. Fatty acids were determined and expressed as % of total fatty acids.

Dietary management practices in phenylketonuria across European centres.

Background: Dietary phenylalanine restriction is the cornerstone of phenylketonuria (PKU) management. However, there are no European consensus guidelines for its optimal dietary care.

Methods: Detailed information on the routine dietary management of PKU was obtained from 10 European centres using structured questionnaires.

Body mass index rebound and overweight at 8 years of age in hyperphenylalaninaemic children.

Aim: To evaluate whether the age at body mass index (BMI) rebound may be associated with overweight at age 8 y in hyperphenylalaninaemic (HPA) children.

Methods: A longitudinal observational study including 97 HPA children born 1984-1993 and detected by the National Neonatal Screening programme. Children were followed up at the same institution and evaluated for dietary intakes and anthropometrical parameters from diagnosis up to the age of 8 y.

Earlier smoking habits are associated with higher serum lipids and lower milk fat and polyunsaturated fatty acid content in the first 6 months of lactation.

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition.

Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy.

Phenylalanine hydroxylase mutations and phenylalanine-tyrosine metabolism in heterozygotes for phenylalanine hydroxylase deficiency.

Unlabelled: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Parents of patients affected by PAH deficiency (n = 25) detected through the Italian Neonatal Screening Program and referred from January 1994 to June 2000, and parents of healthy children were investigated. In total, 68 subjects without any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and gender-matched controls, were recruited.

Polyunsaturated fatty acids in maternal plasma and in breast milk.

In order to explain processes underlying the transfer of fatty acids from the maternal compartment into human milk, the lipid content and the fatty acid composition of maternal plasma and milk have been analyzed in breastfeeding mothers at 1 day and 3 months of lactation. The rise in milk lipids occurring during the study period was concomitant with a fall in plasma total fat content, mainly due to the decrease of triglycerides. Significant correlations between plasma and milk fatty acids at the two time points were observed only for linoleic (LA, 18:2 n-6) and (alpha;-linolenic acid (alpha LNA, 18:3 n-3), while for arachidonic (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) correlations were found only at one day and 3 months, respectively.

Long-chain polyunsaturated fatty acid concentrations in human hindmilk are constant throughout twelve months of lactation.

We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method.

Breastfeeding duration, milk fat composition and developmental indices at 1 year of life among breastfed infants.

The associations of breastfeeding duration and milk fat composition with the developmental outcome at 1 year of age were measured within 44 infants exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12 months for total fat and fatty acid content. Infants were examined at 12 months by means of the Bayley test.

Free glutamine and glutamic acid increase in human milk through a three-month lactation period.

Background: Previous short observational studies on the free amino acid (FAA) content of human milk have shown that glutamine and glutamic acid increase in the first 4 to 6 weeks of life.

Methods: Changes in human milk content of free amino acids (FAAs) was determined at colostrum, 1 month, and 3 months of lactation in 16 healthy lactating women after delivery of full-term infants. Milk was collected at the end of each feeding (hindmilk) during 24 hours.

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study.

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants.