Long-term efficacy of 'ready-to-drink' protein substitute in phenylketonuria

Background:  In phenylketonuria (PKU), protein substitute is an essential part of dietary treatment. Short-term studies have demonstrated that liquid protein substitutes (LPS) are efficacious, and improve compliance in teenagers and adults with PKU, although there are no data available to demonstrate that their effectiveness is sustained over time. The present retrospective study aimed to evaluate the long-term efficacy of ready-to-drink protein substitute in a group of people with PKU.
Methods:  Thirty-four patients (17 females and 17 males, median age 14.9 years, range 7.2–53.8 years) with PKU on dietary management were recruited from Birmingham Children's Hospital. All patients who were taking a LPS for a median of 2.4 years (range 6 months to 4.1 years), had their plasma phenylalanine concentrations, anthropometric and nutritional biochemical markers reviewed, both before and when taking the LPS.
Results:  There was a significant improvement in median plasma phenylalanine ( P  < 0.05), vitamin B₁₂ ( P  < 0.01), calcium ( P  < 0.05) and albumin ( P  < 0.05) concentrations in subjects ( n  = 13) aged >18 years when taking the LPS. In the children aged 7–18 years ( n  = 21), median plasma phenylalanine concentrations were maintained on LPS. Their plasma selenium concentrations ( P  < 0.05) deteriorated, but calcium ( P  < 0.05), albumin ( P  < 0.01), haemoglobin ( P  < 0.01) and haematocrit ( P  < 0.01) significantly improved.
Conclusions:  This retrospective review suggested that, in adult patients, the long-term use of LPS is associated with better compliance by lowering blood phenylalanine and improving nutritional biochemical markers.     

Diet and phenylketonuria: time for change?

This article is a report of a meeting of dietitians held on 15 September 1992 in Birmingham to discuss the recommendations of a 'Medical Research Council Working Party on the Dietary Management of Phenylketonuria'. (Contributions on the day of the meeting came from Judith Houghton, Eleanor Weetch, Isabel Smith, Sheena Laing, Ruth Watling, John Walter, Rodney Pollitt.)     

Abnormal feeding behaviours in phenylketonuria

The strict low phenylalanine diet used in the treatment of phenylketonuria (PKU) may adversely affect feeding behaviour and nutritional status in PKU children. The feeding behaviour of 15 unselected PKU children (12 girls, 3 boys) aged 1–5 years (mean age 3 years) was studied. Each child was matched with an unrelated age- and sex-matched non-PKU control child. All the PKU children were on a strict low phenylalanine diet. The mothers of all the children completed a validated feeding assessment questionnaire examining maternal perceptions of the incidence and type of feeding problems, feeding behaviour and parental management. A scored video recording of each child eating a midday meal was made, and mothers recorded a 3-day dietary assessment. Mothers of PKU children perceived their children to have more feeding problems than the mothers of the control children. They said that they were more likely to have a poor appetite ( P <0.05), and have more gastrointestinal symptoms ( P <0.05). The PKU group were more likely to be given their midday meal separately from the rest of the family (PKU group 67%, control group 20%; P <0.05), were less likely to start their meal without prompting ( P <0.005) and received less parental feeding directed verbalization ( P <0.05). Although there was no significant difference in energy intake between the two groups, the PKU group had a significantly lower weight z score than the control group: median (range) weight for age, PKU group z score −0.81 (−2.23 to 2.21); control group 0.65 (−0.81 to 1.83) ( P <0.05), but no differences were noted for height z score. This study is the first to report on the extent of feeding difficulties in young PKU children. An awareness of the consequences of rigid diet therapy should prove helpful in improving management strategies.     

Changes in serum phenylalanine after overnight fasts in youngsters with phenylketonuria

Background and aims: In patients with phenylketonuria (PKU), overnight fasting is associated with rises in serum phenylalanine (PHE) concentration. This is thought to result from catabolism of endogenous protein, which can be reduced by a bedtime snack accompanied by a dose of PHE-free protein substitute (P/S). This study assessed the effectiveness of this strategy and whether any additional benefit was conferred by omitting PHE from the bedtime snack. Methods: Data are presented for 18 PKU children (aged 9–16 years), studied over a 48-h period whilst following diets of known composition. All the subjects had a bedtime snack accompanied by 25% of their P/S daily requirement. Half the subjects (Group X) had 25% of their daily PHE allowance in the bedtime snack, whilst the others (Group Z) ate only ‘PHE-free’ foods at this time. Results: Overnight changes in serum PHE levels were generally small for both groups; the mean serum PHE level changed very little overnight (Group X: 405 μmol L^?1 post snack, 389 μmol L^?1 prebreakfast; Group Z: 430 μmol L^?1 post snack, 426 μmol L^?1 pre breakfast). Conclusion: Overnight changes in serum PHE levels can be minimized by a bedtime snack accompanied by a proportion of the daily protein substitute. Omission of PHE from the snack confers no extra advantage.     

A survey of feeding practices in infants with phenylketonuria

Background: Although the management of phenylketonuria (PKU) in infancy and early childhood is a critical part of the overall care of the disorder, there are few guidelines on infant feeding in this condition. This survey was undertaken to establish the practices of dietitians from major PKU centres in Australia and the UK. Methods: A postal questionnaire examining infant feeding practices was sent to dietitians at nine major PKU centres in the UK and four in Australia, with each dietitian describing the infant feeding process in their last five infants. A total of 63 infants were investigated. Results: A lower than expected incidence of infants with PKU were breast fed at the time of diagnosis: 28% of infants in the UK and 41% from Australia. Amino acid intake varied between 2.0 g kg^?1 day^?1 to 3.5 g kg^?1 day^?1 with 86% of dietitians calculating total amino acid intake derived from both protein substitute intake and normal infant formula. Amino acid intake was not calculated in breast-fed infants. In breast-fed infants, phenylalanine-free protein substitute was always given before breast feeds. In bottle-fed infants, normal infant formula was given before phenylalanine-free protein substitute in 75% of infants. Solids were usually introduced between 3 and 6 months and phenylalanine-free solids were given initially to the majority of infants. Most problems were seen when introducing a more concentrated phenylalanine-free protein substitute to maintain the required amino acid intake in older infants. Age of introduction varied between 4 and 12 months and type of approach included concentrating infant protein substitutes, use of L -amino acid protein substitutes only, or L -amino acid protein substitutes with added carbohydrate, vitamins and minerals. Conclusions: There appeared to be no uniform policy of infant feeding in PKU and more work is needed correlating practices to develop national and even international protocols for management.     

The determination of phenylalanine content of foods suitable for phenylketonuria

BACKGROUND: A low phenylalanine diet for people with phenylketonuria (PKU) is very restrictive. Natural foods allowed are based chiefly on fruits and vegetables but there is limited analysis on the phenylalanine content of newer and exotic fruit and vegetables. The assumption that 1 g protein yields 50 mg phenylalanine does not apply to fruits and vegetables. METHODS: The National Society for Phenylketonuria Medical Advisory Panel commissioned the phenylalanine analysis of 172 foods, which emphasis on fruit and vegetables. The foods were purchased from retail outlets and analysed by LGC Limited (67 foods) and the LFI (105 foods). RESULTS: There was a strong correlation between this phenylalanine and UK analyses published in 1980, but previous analysis included only a limited range of fruits and vegetables (r = 0.8746; P < 0.0001). There was also correlation between phenylalanine and UK protein analyses (r = 0.7976; P < 0.0001). CONCLUSION: This new phenylalanine data have enabled a wider range of fruits and vegetables to be safely incorporated into the diet of people with PKU.     

Infant feeding: a review of weaning

Current advice on mixed feeding for the infant is reviewed, with reference to recent reports in the UK. Changes in practice are illustrated and the relevance to the infant of current advice for a prudent diet in adulthood is discussed. It is suggested that future reports on infant feeding may need to be more fully extended to the pre-school child.     

Growth and Body Composition in PKU Children—A Three-Year Prospective Study Comparing the Effects of L-Amino Acid to Glycomacropeptide Protein Substitutes

Protein quality and quantity are important factors in determining lean body (muscle) mass (LBM). In phenylketonuria (PKU), protein substitutes provide most of the nitrogen, either as amino acids (AA) or glycomacropeptide with supplementary amino acids (CGMP-AA). Body composition and growth are important indicators of long-term health. In a 3-year prospective study comparing the impact of AA and CGMP-AA on body composition and growth in PKU, 48 children were recruited. N = 19 (median age 11.1 years, range 5–15 years) took AA only, n = 16 (median age 7.3 years, range 5–15 years) took a combination of CGMP-AA and AA, (CGMP50) and 13 children (median age 9.2 years, range 5–16 years) took CGMP-AA only (CGMP100). A dual energy X-ray absorptiometry (DXA) scan at enrolment and 36 months measured LBM, % body fat (%BF) and fat mass (FM). Height was measured at enrolment, 12, 24 and 36 months. No correlation or statistically significant differences (after adjusting for age, gender, puberty and phenylalanine blood concentrations) were found between the three groups for LBM, %BF, FM and height. The change in height z scores, (AA 0, CGMP50 +0.4 and CGMP100 +0.7) showed a trend that children in the CGMP100 group were taller, had improved LBM with decreased FM and % BF but this was not statistically significant. There appeared to be no advantage of CGMP-AA compared to AA on body composition after 3-years of follow-up. Although statistically significant differences were not reached, a trend towards improved body composition was observed with CGMP-AA when it provided the entire protein substitute requirement.     

Dietetic Management of Adults with Phenylketonuria (PKU) in the UK: A Care Consensus Document

There is an increasing number of adults and elderly patients with phenylketonuria (PKU) who are either early, late treated, or untreated. The principal treatment is a phenylalanine-restricted diet. There is no established UK training for dietitians who work with adults within the specialty of Inherited Metabolic Disorders (IMDs), including PKU. To address this, a group of experienced dietitians specializing in IMDs created a standard operating procedure (SOP) on the dietetic management of adults with PKU to promote equity of care in IMD dietetic services and to support service provision across the UK. The group met virtually over a period of 12 months until they reached 100% consensus on the SOP content. Areas of limited evidence included optimal blood phenylalanine reporting times to patients, protein requirements in older adults, management of weight and obesity, and management of disordered eating and eating disorders. The SOP does not include guidance on maternal PKU management. The SOP can be used as a tool for training dietitians new to the specialty and to raise the standard of education and care for patients with PKU in the UK.     

The struggle of weaning: Factors determining breastfeeding duration in East Bhutan

This paper presents the qualitative part of a project in a traditional community in East Bhutan, which, among other items, investigates the effects on child health of breastfeeding, weaning and subsequent pregnancy of the mother. Quantitative data from the project have shown that children who are weaned during a subsequent pregnancy of the mother have a reduced weight gain and an increased incidence of infectious diseases during weaning, while this is not so for children weaned from non-pregnant mothers. In-depth interviews with 35 women with experience from breastfeeding were carried out in the local language in order to obtain qualitative data regarding the processes underlying the mother decisions during weaning. Breastfeeding was found to fulfil a valuable social function in addition to its biological and emotional properties. The breastfed child had an undebatable “right of access” to the mother's care, not only her breast, whenever it wanted. This child also assumed a status in the family in which both its vulnerability, its special needs and its value were clearly recognized. The mothers expressed a basic motivation to breastfeed “as long as possible”. There were, however, important limitations as to how this was manifested in the practical weaning process. If the mother was pregnant at the time of weaning, these limitations tended to be mother-centred. Most of the women had experienced tenderness of the breasts and a reduced milk production from the start of the next pregnancy. It was believed that the breast milk of a pregnant woman could “rot” and cause disease in the child. In spite of this belief, concurrent breastfeeding and pregnancy were common, but a pregnant mother whose breastfed child got ill, e.g. with diarrhoea, would immediately stop breastfeeding. The child would thereby abruptly loose the most important protection against the negative effects of the disease, when this protection was most needed. Concurrent pregnancy and lactation are common in many areas of the poor world. This has important consequences for the health of mothers and children, and has only recently been given the attention it derserves.     

高苯丙氨酸血症1 066例随访分析

【目的】 了解高苯丙氨酸血症(hyperphenylalaminemia, HPA)患者治疗随访及预后。 【方法】 对在本院诊断治疗的1 066例HPA的治疗随访结果进行回顾性分析。 【结果】 1)在1 066例HPA患儿中,共有1 016例为苯丙氨酸羟化酶缺乏症,即经典型苯丙酮尿症(phenylketonuria, PKU),50例为四氢生物蝶呤缺乏症(tetrahydrobiopterin deficiency, BH₄D)。在这些PKU患者中,有369例(34.62%)患儿在新生儿筛查时被确诊并在3个月内开始规律治疗,241例(22.61%)在生后3～12个月内确诊, 456例(42.78%)在1岁后才确诊。2)3个月内筛查治疗的患儿智力发育明显高于非筛查确诊的患儿(96±15, 69±11;t=14.19,P＜0.01﹚。3)3个月后才确诊的经治疗后智力水平也有明显提高﹙46±15,69±11,t=7.13,P＜0.05﹚。4)氢质子磁共振波谱(¹HMRS)检测22例HPA患儿的脑苯丙氨酸(phenylalanine, Phe)浓度表明患儿血、脑Phe浓度与智商均呈负相关关系(r_血=0.505,r_脑=0.647,P<0.01)。 【结论】 对所有HPA患者均应进行鉴别诊断,尽早确诊和治疗, 控制血、脑苯丙氨酸浓度是减少智能落后的有效措施。     

饮食治疗苯丙酮尿症患儿全血钙及微量元素水平分析

【目的】　探讨低苯丙氨酸饮食对苯丙酮尿症 ( phenylketonuria ,PKU)患儿血钙 (Ca)及微量元素铁、铜、锌、硒、铬、锰、镉、铅、碘 (Fe、Cu、Zn、Se、Cr、Mn、Cd、Pb、I)的影响。　【方法】　采用电感耦合等离子体质谱仪 (ICP MS)对 3 2例PKU患儿全血钙及微量元素进行测定 ,并以 46名正常儿童的全血水平作为正常值对照。　【结果】　PKU患儿全血Ca及微量元素Fe、Zn、Se、Cr、Mn、Pb、I明显低于正常儿童对照组 (P <0 .0 5 ) ,血Cu、Cd与对照组相比差异无显著性 (P >0 .0 5 )。　【结论】　对低苯丙氨酸 (Phe)饮食治疗的PKU患儿有必要检测血钙和微量元素水平 ,并及时补充以纠正低苯丙氨酸饮食治疗过程中这些元素的摄入不足 ,保证患儿得到全面营养     

Quality evaluation of rice bran protein isolate-based weaning food for preschoolers

Agro–industrial waste ‘rice bran’ was stabilized and the extracted protein isolates were used as ingredients to make nutritive complimentary food for the growing infants. The formulation processed through drum drying and the starchy ingredients were pregelatinized to reduce bulk in the prepared meal and facilitate spoon-feeding. The formulations had uniform texture, light golden color and good paste consistency. Nutrient composition was good enough to meet standards for supplementary infant foods. Caloric value remained up to 416 kcal/100 g with spoonable viscosity and 80.90–84.45% in vitro digestibility. A single meal could substantially contribute to the daily essential amino acid requirement. The formulation had good acceptability during a short-term infant-feeding trial. The present study can provide practical guideline for manufacturers as well as the nutritionist for the use of an economical and nutritive formulation for young children.     

Knowledge,compliance and serum phenylalanine concentrations in adolescents and adults with phenylketonuria and the effect of a patient‐focused educational resource

Background There is a lack of dedicated resources for adolescent and adult patients with phenylketonuria (PKU) and few studies have examined dietary practices within this group. Methods One hundred and seventy‐seven PKU patients were sent questionnaires to assess dietary compliance and the preferred format for an educational resource. Seventy‐one patients responded; 32 following diet were recruited to assess the resource’s impact on test variables. The results were compared for the intervention group (n = 22) and control group (n = 10) at baseline, and 1 and 6 months after resource intervention. Results Most patients were aware of dietary recommendations, although this did not always result in compliance. The preferred resource format was a filofax‐style folder with inserts (P < 0.05). There was a significant difference in the extent of change in knowledge score between baseline and 1 month in favour of the intervention group (P < 0.05). The improvement in knowledge was not accompanied by a significant improvement in measures of compliance. Conclusions These findings add to the knowledge base about this patient group and support the use of patient involvement in resource development. It is likely that the test parameters used were not sensitive enough to pick up subtle and longer‐term effects on compliance.     

The development of nonweighed pilot methods for estimating phenylalanine exchanges in non‐phenylketonuria volunteers

Background: In children with phenylketonuria (PKU), the daily weighing of the phenylalanine allowance from food is advocated. There is a need to develop nonweighed methods of measuring dietary phenylalanine, aiming to ease caregiver burden and possibly improve dietary adherence. The accuracy of three methods (household measures, digital photographs and weighing) for measuring 50‐mg phenylalanine exchanges for PKU was investigated in a randomised, controlled trial. Methods: There were 51 volunteers (32 females; 19 males; median age: 34 years, range 13–77 years), who were all unconnected with PKU. For three consecutive days, all volunteers attended a research centre and, each day, were randomly allocated a different method (household measures, digital photographs and weighing) for phenylalanine exchange measurement. On each day, they measured the amount of food equivalent to one 50‐mg phenylalanine exchange for 24 common foods. All phenylalanine exchange samples (3672 samples) were then reweighed by the investigators. Results: No method of measuring 50‐mg phenylalanine exchanges was accurate when used by volunteers. The median percentages (range) of all food samples within 10% of target were only 67% (41–98), 44% (4–96) and 41% (4–98) for weighing, household measures and photographs, respectively. The respective median (range) of samples within 20% of the target weights were: 96% (51–100) weighing, 82% (10–100) photographs and 80% (6–100) household measures. No noteworthy difference in accuracy was observed between household measures and photographs. Conclusions: Volunteers not associated with PKU could not measure 50‐mg phenylalanine exchanges accurately using weighing, household measurements or photographs. Therefore, it is important to consider developing methods for improving accuracy of measurement of 50‐mg phenylalanine exchanges in PKU.