Does maternal knowledge and parent education affect blood phenylalanine control in phenylketonuria?

BACKGROUND: Metabolic control in phenylketonuria (PKU) may be influenced by parental ability because dietary treatment involves complex food choices. This is an observational study to compare maternal carer (MC) knowledge and parental education with phenylalanine concentrations in children with PKU. METHODS: Children (n = 46; 26 boys) aged 1-10 years (median age 6 years) on dietary treatment were recruited. Their median lifetime and median phenylalanine concentrations in the year prior to study were estimated. MC completed a questionnaire to assess dietary knowledge. RESULTS: Overall maternal knowledge on most aspects of diet was good and there was a correlation between annual median blood phenylalanine concentrations, but at the age of 5-6 years of age only, and higher maternal carer scores on PKU knowledge (r = -0.646; P < 0.0001). Three of only four children (12%) with median phenylalanine concentrations above 500 micromol L(-1) in the year prior to study had both parents leave school without educational qualifications. Children who had median phenylalanine concentrations (n = 3; 7%) over the recommended ranges at 3 years of age or earlier continued to have poor control. CONCLUSIONS: Blood phenylalanine control within the first 3 years of age, poor parental educational achievement at school level, and unsatisfactory maternal dietary knowledge may all influence longer-term blood phenylalanine control in children.

Protein substitute dosage in PKU: how much do young patients need?

BACKGROUND: The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). AIM: To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) METHODS: In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). RESULTS: When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. CONCLUSIONS: A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Protein substitutes for PKU: what's new?

Protein substitutes are an essential component in the management of phenylketonuria. A series of studies at Birmingham Children's Hospital have investigated their optimal dosage, timing and practical administration as well as the efficacy and tolerance of novel protein substitutes. The key findings are as follows. (1). Lower dosages of protein substitute (1.2 g/kg per day of protein equivalent) adversely affect blood phenylalanine control in children aged 1-10 years. (2). There is wide variability in 24 h blood phenylalanine concentrations. (3). Adjusting protein substitute timing during daytime does not reduce blood phenylalanine variability. (4). Repeated 4 h administration of protein substitute throughout 24 h markedly reduces phenylalanine variability and leads to lower phenylalanine concentrations. (5). The new, concentrated, low-volume protein substitutes and amino acid tablet preparations are efficacious and well tolerated by patients. (6). Administration of protein substitute as a gel or paste has reduced difficulties with administration of protein substitute in children. These findings are important in rationalizing treatment strategies, improving patient compliance and overall in improving blood phenylalanine control.

A new, low-volume protein substitute for teenagers and adults with phenylketonuria.

Some older patients with phenylketonuria (PKU) fail to consume their protein substitute (with or without vitamin and mineral supplements) in prescribed amounts, which contributes to poor blood phenylalanine control. PKU Express (Vitaflo), is a new low-volume (amino acids 72 g/100 g), low-carbohydrate, phenylalanine-free protein substitute with added vitamins and minerals designed for people with PKU over 8 years of age. In an open intervention study, the aim was to investigate its acceptability and effectiveness in a group of teenagers and adults with PKU. Twenty-three subjects (15 female; 8 male) with PKU, who had a median age of 17 years (range 8-37 years) took the substitute for 8 weeks. A 3-day prospective diet diary, height, weight, plasma amino acids, biochemical and haematological nutritional analytes were measured at weeks 0 and 8. Skin-puncture bloods for plasma phenylalanine were collected every 2 weeks. The median weight of protein substitute (with or without vitamin and mineral supplements) consumed decreased by 33% from 150 g (range 140-180) daily to 100 g (range 100-125) daily ( p <0.001). Median change in energy intake decreased by a median of 10% (95% CI 2.0 to 18.0) when compared to intake on original protein substitute. On PKU Express, the intakes of all nutrients exceeded the dietary reference values but none was excessively high. Blood phenylalanine decreased by a mean of 37 micromol/L (95% CI-27 to 102) during the trial. Body mass index decreased in 40% of subjects. Changes in blood phenylalanine or body mass index were not statistically significant. Most of the nutritional, haematological and biochemical indices stayed within normal reference ranges for the analytes studied. Sixteen (70%) of the subjects had low plasma selenium at the start, but only 13 (57%) at the study end. Plasma vitamin B12 was high in 8 subjects at the start of the study and 9 at the end. Twenty-one subjects (96%) stated that the product was convenient and easy to prepare. However, 7 (32%) described the smell and 9 (46%) the texture as the same as or worse than those of previous protein substitutes. Because of the use of the premeasured sachets, some subjects were able to prepare their own protein substitute for the first time. PKU Express is a safe, efficacious, protein substitute that significantly reduces the daily volume of prescribed protein substitute.

Administration of protein substitute and quality of control in phenylketonuria: a randomized study.

Uneven administration of an L-amino acid protein substitute is an important contributing factor in variability in plasma phenylalanine concentrations over the 24-hour period in patients with phenylketonuria under treatment. The aim of this study was to determine whether manipulating the timing of protein substitution would reduce variability in plasma phenylalanine over 24 h. Sixteen children (aged 1-11 years) with well-controlled phenylketonuria were entered into a randomized crossover study in which four protocols of the same daily dose of protein substitute administration were compared. In protocol A, three equal, divided doses were given with meals over 10 h; in protocol B, three equal doses over 14 h; in protocol C, four equal doses over 14 h; and in protocol D, six equal doses over 24 h (3 subjects only). Four-hourly skin puncture blood specimens were collected for 48 h in each study protocol. In protocols A, B and C, but not in protocol D, there was wide variability in 24 h plasma phenylalanine. The median daily differences (micromol/L) between highest and lowest phenylalanine concentrations were: for protocol A, 140; for protocol B, 100; for protocol C, 120; and for protocol D, 40. In protocol D, 97% of all phenylalanine concentrations were below 120 micromol/L and no concentration fell below 40 micromol/L. Administration of protein substitute overnight as well as during daytime produces stable and lower plasma phenylalanine concentrations and may lead to improved dietary phenylalanine tolerance.

Free use of fruits and vegetables in phenylketonuria.

This study aimed to evaluate systematically the effect of the free use of fruits and vegetables containing an intermediate amount of phenylalanine (51-100 mg/100 g) on the biochemical control in children with phenylketonuria (PKU). Fifteen subjects with PKU, with a median age of 6 years (range 1-24 years) were studied. In a three-part prospective 15-week study, subjects sequentially ate fruits and vegetables containing phenylalanine 0-50 mg/100 g for weeks 1 to 3; 51-75 mg/100 g for weeks 4 to 8; and 76-100 mg/100 g for weeks 9 to 15. Plasma phenylalanine concentrations were measured twice daily for three consecutive days in weeks 1, 3, 6, 8, 11, 13 and 15. A standard menu was followed on the blood sampling days. Daily dietary records of fruits and vegetables under study were kept throughout the trial. Control of phenylalanine concentrations was not adversely affected by the free use of fruits and vegetables containing 51-100 mg/100 g. Pre-breakfast median plasma concentrations were: weeks 1 to 3, 260 micromol/L (range 90-890); weeks 4 to 8, 255 micromol/L (range 130-920); and weeks 9 to 15, 278 micromol/L (range 30-880). Pre-evening meal median plasma phenylalanine concentrations were: weeks 1 to 3, 240 micromol/L (range 30-820); weeks 4 to 8, 210 micromol/L (40-880); and weeks 9 to 15, 238 micromol/L (range 20-880). These data suggest that free use of fruits and vegetables containing 51-75 mg/100 g poses no problem for children with PKU.

Are tablets a practical source of protein substitute in phenylketonuria?

BACKGROUND: A phenylalanine-free amino acid based protein substitute is necessary to provide the major source of protein in phenylketonuria (PKU). Protein substitutes in PKU are usually given as drinks. These are unpalatable and compliance is often poor. Tablets containing a suitable mixture of phenylalanine-free amino acids (Aminogran Food Supplement, UCB) are now available. AIMS: To compare the effectiveness and acceptability of these tablets with conventional protein substitute drinks. METHODS: Twenty one subjects with PKU, aged 8-25 years, participated in a randomised crossover study. During one phase, subjects received at least 40% of their protein substitute requirements from the amino acid tablets and the rest from their usual protein substitute tablets. During the other phase, they received their usual protein substitute. Each period lasted 12 weeks. Blood phenylalanine concentrations were measured at least once every two weeks and other plasma amino acids were measured at the beginning, at crossover, and at the end of the study. The subjects kept a diary of all protein substitute taken. RESULTS: Compliance appeared to be better with the new tablets than with patients' usual protein substitutes. Ninety per cent (18/20) recorded that they took the tablets as prescribed, compared with 65% (13/20) fully compliant with their usual protein substitute. Moreover, plasma phenyalanine was lower on the amino acid tablets, and the median difference in blood concentrations between the two groups was 46 micro mol/l (95% CI 14.8 to 89.0, p = 0.02). Tyrosine increased by a median of 16 micro mol/l daily on the amino acid tablets (95% CI 7.1 to 40.5, p = 0.01). Most subjects (70%) preferred incorporating the new tablets into their usual protein substitute regimen. CONCLUSIONS: Amino acid tablets are an effective and relatively popular protein substitute in older children, teenagers, and adults with PKU.

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 mumol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of children below 11 years, three having concentrations < 30 mumol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = -0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.

Factors affecting the variation in plasma phenylalanine in patients with phenylketonuria on diet.

The optimal dietary management of children with phenylketonuria (PKU) has rarely been rigorously explored. The aim of this study was to assess longitudinally the effects of three factors thought to influence plasma phenylalanine concentrations in PKU: total energy intake; protein intake from natural foods allowed freely in addition to allocated phenylalanine exchanges; and the distribution of protein substitute throughout the day. Nineteen subjects, 15 girls and four boys aged 1-16 years, were enrolled. Food intake was weighed, and twice daily plasma phenylalanine concentrations measured during either 3-day or 4-day periods, for a total of 21 days throughout six months. There was a negative correlation between the percentage of protein substitute eaten by the time of the evening meal and the fall in plasma phenylalanine concentration during the day (r = -0.941; p < 0.0001). On average, 49% of pre-evening meal plasma phenylalanine concentrations were less than 100 mumol/l in children who had taken at least 65% of their protein substitute by the time of their evening meal. There was no correlation between excess natural protein intake from freely allowed foods and (a) pre-breakfast or pre-evening meal plasma phenylalanine concentrations or (b) the daily change between pre-breakfast and pre-evening meal concentrations. Nor was there any correlation between excess natural protein intake on the previous day and plasma phenylalanine concentration on the following morning. Energy intake was not correlated with plasma phenylalanine concentrations. It is therefore preferable to distribute the protein substitute evenly through the day in order to achieve stable phenylalanine concentrations, rather than to carry out further fine manipulation of the phenylalanine intake, which would make management of the diet even more difficult.

Feeding problems in young PKU children.

Behavioural feeding problems were found to be more prevalent in a group of 15 PKU children aged 1-5 years when compared to non-PKU controls. The parents of PKU children identified poorer apatites (p < 0.01), a more limited range of foods consumed (p < 0.03) and more gastrointestinal symptoms such as vomiting and constipation (p < 0.03) than control children. The children were slower to feed (p < 0.03), were more likely to dislike sweet foods and some ate separately from the rest of the family at mealtime (p < 0.03). The effects on normal feeding behaviour should be considered when advocating strict diet therapy for young PKU children.