Phenylketonuria patients' and their parents' knowledge and attitudes to the daily diet - multi-centre study.

BACKGROUND: The aim of the study was to assess both patients' and their parents' knowledge of phenylketonuria (PKU) treatment and compliance with PKU diet. METHODS: The study included 173 PKU patients aged 10-19 and 110 parents of PKU children who were enrolled in the study on the basis of questionnaire data. The study also included 45 patients aged ≥20. RESULTS: Our study demonstrated that only 45% (n = 74) of PKU patients knew daily Phe intake recommendations, 27% of patients (n = 41) knew the Phe content in a minimum of three out of four researched food products. Patients' knowledge concerning Phe intake (p = 0.0181) and the knowledge of selected food products (p = 0.041819) improved with age. We did not establish such a correlation in the group of PKU children's parents. Approximately 31% of patients and 22% of parents reported helplessness, which increased with the child's age, associated with the necessity to adhere to the diet; 30% of patients reported feeling ashamed of the fact that they could not eat all food products. Regardless of age, children were more likely than parents to report helplessness (p = 0.032005). Among patients, 41.40% declared that they would wish to select products unassisted but their parents did not permit them to do so. The question of whether parents teach children self-reliance in meal preparation was answered affirmatively by 98% of parents and only 81% of children (p = 0.0001). CONCLUSION: Our data demonstrated that parents' and children's knowledge concerning treatment recommendations and food products does not have a direct impact on attitude to the PKU diet. Limiting children's independence in meal selection, growing helplessness in the face of dietary adherence and shame resulting from the necessity to follow a different diet observed in PKU families are responsible for shaping and perpetuating a consistently negative attitude to the diet. The care of PKU paediatric patients requires consistent, long-term family and individual therapy which may counteract the effects of learned helplessness. In regard to the educational effort, a good parent-child relationship as well as the teaching of behaviours motivating patients to comply with the diet are of great importance.

Phenylketonuria patients' and their parents' acceptance of the disease: multi-centre study.

PURPOSE: Phenylketonuria (PKU) still poses a therapeutic challenge for patients and medical professionals. The aim of the study was to assess both patients' and their parents' acceptance of the disease. METHODS: The study included 218 PKU patients and 178 parents of PKU children who were enrolled in the study on the basis of questionnaire data. RESULTS: Regarding attitude towards the disease, our study demonstrated that 63 (28.9 %) PKU patients did not accept the disease. Patients who found accepting the disease difficult, more frequently perceived themselves as inferior/different in comparison with their peers. In total, 36 % of patients did not want their friends to be aware of their condition, while only 18 % of parents believed that their children's peers should not know about their disease. In total, 42 % of parents wanted to talk to other parents of PKU children and only 13 % to a doctor. Only 20 % of patients saw the need to discuss their condition with a doctor. In total, 8 % of children, regardless of age, and 14 % of parents preferred to talk to a psychologist. CONCLUSION: Our data demonstrated that disease acceptance played an essential role in patients' social integration. The study also indicated the need to overcome communication barriers between patients and their healthy peers and for patients to find the courage to be open about the disease. The importance of support groups for PKU families and the significance of strict cooperation between patients and their families with PKU treatment teams were also revealed.

Impact of lipophilic antioxidants and level of antibodies against oxidized low-density lipoprotein in Polish children with phenylketonuria.

The treatment of phenylketonuria (PKU) patients constitutes a phenylalanine (Phe) intake restriction in their diet, which is achieved by adding a special Phe-free amino acid mixture to the diet. It has been reported that this diet could have some micronutrient deficiency. Several authors have also reported an increased oxidative stress or impaired antioxidant status in human and experimental PKU. Our project assessed the concentrations of retinol, alpha-tocopherol, coenzyme Q10, and anti-oxidized low-density lipoprotein (ox-LDL) antibodies in PKU children's plasma. It was found that retinol concentration in PKU children remains within the norm despite a low intake. The lower plasma alpha-tocopherol concentration in PKU children compared with normal children was associated with the lower level of antibodies against ox-LDL. This raises the question whether higher than observed circulatory alpha-tocopherol is indeed beneficial to lower plasma ox-LDL levels. Further studies are needed to explain the genetic factor in PKU patients (e.g., CD36/FAT polymorphism gene). The open clinical question is whether daily supplementation of alpha-tocopherol changes the PKU patients' level of antibodies against ox-LDL.

[Recommendations of prophylaxis of vitamin D deficiency in Poland (2009)]. / Zalecenia dotyczace profilaktyki niedoborów witaminy D w polsce (2009).

Adequate vitamin D intake and its status as well outdoor physical activity are important not only for normal bone development and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. National Consultants and experts in this field established the Polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women based on current literature review. Taking into consideration pleyotropic vitamin D action and safety aspects serum 25-hydroxyvitamin D (25-OHD) level of 20-60 ng/ml (50-750 nmol/l) in children and 30-80 ng/ml (75-200 nmol/I) in adults is considered as optimal. Sunlight exposure inducing vitamin D production in the skin is main endogen source of vitamin D in the body but sunscreens may reduce skin synthesis by 90%. In Poland, skin synthesis is effective only from April to September so other sources of vitamin D such as diet and supplements play an important role. All newborns should be supplemented with 400 IU/d of vitamin D beginning from the first few days of life and continue during infancy. In formula fed infants vitamin D intake from the diet should be taken into account. In preterm infants higher total vitamin D intake (400-800 IU/day) is recommended till 40 weeks post conception. Total vitamin D intake in children and adolescents required from all sources (diet and/or supplements) should be 400 IU/d between October and March and throughout the whole year in case of inadequate vitamin D skin synthesis during the summer months. In overweight/obese children supplementation with higher dosage of vitamin D up to 800-1000 IU/d should be considered. Adults require 800-1000 IU/d of vitamin D. In pregnant and lactating women such supplementation is recommended in case of inadequate intake from diet and/or skin synthesis supplementation. Monitoring of serum 25-OHD level to define optimal dosage should be considered.

[Prophylaxis of vitamin D deficiency--Polish recommendations 2009]. / Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D--2009.

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.

[Prophylaxis of vitamin D deficiency--Polish recommendation 2009]. / Stanowisko Zespolu Ekspertów. Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D - 2009.

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.

Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the ability of sapropterin dihydrochloride (pharmaceutical preparation of tetrahydrobiopterin) to increase phenylalanine (Phe) tolerance while maintaining adequate blood Phe control in 4- to 12-year-old children with phenylketonuria (PKU). STUDY DESIGN: This international, double-blind, randomized, placebo-controlled study screened for sapropterin response among 90 enrolled subjects in Part 1. In Part 2, 46 responsive subjects with PKU were randomized (3:1) to sapropterin, 20 mg/kg/d, or placebo for 10 weeks while continuing on a Phe-restricted diet. After 3 weeks, a dietary Phe supplement was added every 2 weeks if Phe control was adequate. RESULTS: The mean (+/-SD) Phe supplement tolerated by the sapropterin group had increased significantly from the pretreatment amount (0 mg/kg/d) to 20.9 (+/-15.4) mg/kg/d (P < .001) at the last visit at which subjects had adequate blood Phe control (<360 micromol/L), up to week 10. Over the 10-week period, the placebo group tolerated only an additional 2.9 (+/-4.0) mg/kg/d Phe supplement; the mean difference from the sapropterin group (+/-SE) was 17.7 +/- 4.5 mg/kg/d (P < .001). No severe or serious related adverse events were observed. CONCLUSIONS: Sapropterin is effective in increasing Phe tolerance while maintaining blood Phe control and has an acceptable safety profile in this population of children with PKU.

[Concentration of osteoprotegerin, bone formation and resorption markers in patients with phenylketonuria]. / Stezenie osteoprotegeryny oraz markerów kosciotworzenia i resorpcji kosci u chorych na fenyloketonurie.

UNLABELLED: Non-invasive biochemical markers which show global skeletal activity have lately been developed and validated for the assessment of bone formation and bone resorption processes. Among them, osteocalcin (OC) and collagen type I cross-linked C-telopeptide (CTX) are considered to be clinically useful. Recently the novel cytokine osteoprotegerin (OPG), belonging to the tumour necrosis factor receptor family, has been established as an endogenous inhibitor of osteoclastogenesis and resorption processes. Some authors have observed decreased bone mineral density and osteopenia in patients suffering from phenylketonuria (PKU). The aim of the study was to assess osteoprotegerin and some bone formation and resorption markers concentrations in phenylketonuric patients. MATERIAL AND METHODS: We measured OPG, OC and CTX in 112 patients with PKU treated at the Department of Pediatrics of the Institute of Mother and Child in Warsaw. Healthy subjects in the same age range sent to our laboratory for routine analytical control were the reference group. Serum bone metabolism markers were determined by an immunoenzymatic assays. RESULTS: Mean serum level of OPG was significantly lower in PKU patients than in controls: in prepubertal and postpubertal subjects by about 15% and in adolescents by 35% respectively. Serum OC and CTX in prepubertal children with PKU compared to the control group was lower by 20-25%. In adolescents both markers were slightly lower (by about 10%) and in postpubertal subjects OC was lower by 25% and CTX by 15% compared to the age-matched controls. CONCLUSIONS: Our results indicate that in phenylketonuric patients an imbalance between bone formation and degradation processes occurred and they are at risk for osteopenia and osteoporosis in later life.

Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study.

BACKGROUND: Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation. We aimed to test the efficacy of sapropterin, a synthetic form of tetrahydrobiopterin (BH4), for reduction of blood phenylalanine concentration. METHODS: We enrolled 89 patients with phenylketonuria in a Phase III, multicentre, randomised, double-blind, placebo-controlled trial. We randomly assigned 42 patients to receive oral doses of sapropterin (10 mg/kg) and 47 patients to receive placebo, once daily for 6 weeks. The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks. Analysis was on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT00104247. FINDINGS: 88 of 89 enrolled patients received at least one dose of study drug, and 87 attended the week 6 visit. Mean age was 20 (SD 9.7) years. At baseline, mean concentration of phenylalanine in blood was 843 (300) micromol/L in patients assigned to receive sapropterin, and 888 (323) micromol/L in controls. After 6 weeks of treatment, patients given sapropterin had a decrease in mean blood phenylalanine of 236 (257) micromol/L, compared with a 3 (240) micromol/L increase in the placebo group (p<0.0001). After 6 weeks, 18/41 (44%) patients (95% CI 28-60) in the sapropterin group and 4/47 (9%) controls (95% CI 2-20) had a reduction in blood phenylalanine concentration of 30% or greater from baseline. Blood phenylalanine concentrations fell by about 200 micromol/L after 1 week in the sapropterin group and this reduction persisted for the remaining 5 weeks of the study (p<0.0001). 11/47 (23%) patients in the sapropterin group and 8/41 (20%) in the placebo group experienced adverse events that might have been drug-related (p=0.80). Upper respiratory tract infections were the most common disorder. INTERPRETATION: In some patients with phenylketonuria who are responsive to BH4, sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylalanine diet, and might even replace the diet in some instances.

[Whole blood citrulline levels in patients with coeliac disease]. / Stezenia cytruliny w pelnej krwi u chorych na celiaki.

UNLABELLED: Citrulline is a non-protein amino acid synthesized by the intestine. Whole blood citrulline concentrations in patients with coeliac disease have not been reported. The aim of the study was determination of the amino acid concentrations in coeliacs on gluten-free diet and gluten-containing diet. MATERIAL AND METHODS: 61 patients with coeliac disease were studied. Whole blood citrulline were determined in dried blood spots by tandem mass spectrometry. One-way analysis of variance and the Bonferroni post hoc test for multiple comparisons were used to determine differences among groups under study. RESULTS: Mean citrulline levels were higher in patients on strict gluten-free diet comparing to those newly diagnosed (32.2 +/- 8.7 vs. 24.9 +/- 5.7 micromol/l; p = 0.025). CONCLUSION: Whole blood citrulline concentration may be a simple biochemical marker for diagnosis and monitoring enterocyte loss in coeliac disease.

Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations.

BACKGROUND: Most cystic fibrosis (CF) patients develop steatorrhea and require pancreatic enzyme replacement therapy. However, there are few data regarding the decline of exocrine pancreatic function within the first years of life in relation to CF genotype. We assessed the decline of pancreatic function in CF infants carrying class 1 or 2 CFTR mutations who were diagnosed in a neonatal screening program. MATERIALS AND METHODS: Twenty-eight CF patients were included in the study and 27 completed the study. In all subjects, fecal pancreatic elastase-1 concentrations and fecal fat excretion were scheduled to be determined at diagnosis, at 6 months of age and subsequently at 6-month intervals. RESULTS: In all CF patients, fecal pancreatic elastase-1 concentrations of the first assay after diagnosis (3 to 4 months of age) were lower than the cut-off level for normals of <200 microg/g stool. Steatorrhea was found in 81.5% of these subjects. At the age of 6 months, all screened CF subjects had fecal pancreatic elastase-1 concentrations <100 microg/g and at the age of 12 months all were pancreatic insufficient. At that time, having proved pancreatic insufficiency in all studied subjects, we stopped the scheduled further assessment. CONCLUSION: CF patients require careful monitoring of pancreatic status from diagnosis onwards. In patients carrying class 1 or 2 CFTR mutations, pancreatic insufficiency develops in the first months of life. The proper assessment of pancreatic insufficiency and intestinal malabsorption is crucial for the early introduction of pancreatic enzymes.

Serum lipase after secretin stimulation detects mild pancreatic involvement in cystic fibrosis.

BACKGROUND: The assessment of severe pancreatic insufficiency in cystic fibrosis (CF) is not a diagnostic problem. However, identification of mild cases remains a challenge. The aim of this study was to assess the ability of serum lipase after secretin stimulation to identify mild pancreatic insufficiency in patients with CF. MATERIAL AND METHODS: Thirty patients with CF and pancreatic insufficiency (CF-PI) and 30 patients with CF and pancreatic sufficiency (CF-PS) were studied. Thirty healthy subjects with no known gastrointestinal disease served as controls. In all subjects, fecal fat excretion, fecal elastase-1 (E1) concentration and basal and secretin-stimulated serum lipase concentration were measured. RESULTS: All patients with CF-PI and 3 with CF-PS had abnormally low fecal E1 concentrations. The remaining 27 CF-PS patients and all controls had normal values. Basal and post-stimulation lipase levels were extremely low in patients with CF-PI. Mean basal and poststimulation serum lipase concentrations were significantly higher in CF-PS who had normal fecal E1 concentrations but were still below those of controls (P < 0.001). Among the 27 CF-PS patients with normal fecal elastase, high basal and poststimulation lipase values were found in 6 and 17 patients respectively. CONCLUSION: In patients with CF-PS who have normal fecal elastase-1 concentration, the measurement of basal or secretin-stimulated lipase levels might be helpful in identifying the progression of the destructive process in the pancreas.

[Low concentration of alpha-tocopherol in erythrocytes of atopic dermatitis patients]. / Niskie stezenie alpha-tokoferolu w erytrocytach u chorych z atopowym zapaleniem skóry.

BACKGROUND: It is suggested that the lipophilic antioxidant alpha-tocopherol could be useful in the management of atopic dermatitis (DA). AIM: The purpose of the study was to investigate vitamin E (alpha-tocopherol) status in children with DA. MATERIAL AND METHODS: 25 children with DA and 18 healthy controls were enrolled in this study (age: 1-9 years). The concentrations of alpha-tocopherol in plasma and in erythrocytes were determined by high-performance liquid chromatography. t-Student test was used in analysis of results. RESULTS: There were no differences between mean plasma alpha-tocopherol content (19.44 +/- 4,61 mmol/l vs 18.74 +/- 3.38 mmol/l; p>0.05) and the ratio of alpha-tocopherol to total cholesterol in plasma (4.46 +/- 0.60 mmol/mmol vs 4.37 +/- 1,09 mmol/mmol; p>0.05) in patients and controls. Mean concentration of alpha-tocopherol in erythrocytes was significantly lower in children with DA (2.14 +/- 0.69 mmol/L) than in the control group (3.17 +/- 0.49 mmol/L, p<0.001). CONCLUSION: In children with DA, the homeostasis of alpha-tocopherol is changed. Decreased erythrocyte levels of the vitamin are probably due to the limited tissue reserve. The role of vitamin E in the pathogenesis and prevention of DA needs further investigations.

[Toxocariasis - an underestimated problem in paediatrics]. / Toksokaroza--niedoceniany problem w praktyce pediatrycznej.

Aspects of Toxocara spp. epidemiology and paratenic infestation of children are described. Human toxocariasis is caused by infestation of zoonotic roundworms of dogs and cats. Soil sampling showes widespread contamination of the environment, particularly parks and playgrounds, with the eggs of Toxocara spp. Toxocara seroprevelance values in children vary between 3.5% in the West Poland and 19% in the South-East Poland. Children more frequently have clinical symptoms o the disease because of the closer contact with contaminated soil in sand-boxes and relatively frequent geophagia. A 3 years old girl with covert toxocariasis is described. As this case illustrates, this disease can be present without its classic visceral, ocular or neurological manifestations. On admission to the hospital the results of blood tests were as follows: white blood cells count, 43x10(3)/ mm3 (norm <13x10(3)) and hyperosinophilia, 81%. The girl was treated with albendazole 15 mg/kg for five days, after one year the treatment was repeated. The patient was followed with blood samples throughout a period of one and half year. During that time results of serological tests for Toxocara canis were strongly positive. The lowest blood count was 20.0x10(3)/mm3 and eosinophilia, 19%. Possible association between high eosinophilia in toxocariasis and development of allergic and cardiovascular diseases is discussed.

[Hyperhomocysteinaemia in a coeliac disease heterozygote for the two common mutations (677C->T and 1298A->C) of the methylenetetrahydrofolate reductase gene. Case report]. / Hiperhomocysteinemia u chorej na celiakie z polimorficznymi allelami (677C-->T I 1298A-->C) genu reduktazy metylenotetrahydrofolanowej w ukladzie heterozygotycznym--opis przypadku.

A 17 year old girl with coeliac disease was found to have hyperhomocysteinaemia (fasting plasma total homocysteine concentration - 19.93 micromol/L; N<12.75 micromol/L). At the age of 1 5 she gave up gluten-free diet and had only subtle signs of chronic malabsorption such as folic acid and iron deficiency. The patient was heterozygote for both common mutations (677C->T and J298A->C) of the methylenetetrahydrofolate reductase gene. On gluten diet an intake of 5 mg folic acid/d from supplements for two weeks resulted in an increase in serum folate and a reduction in homocysteine concentration (13.20 micromol/L). The patient continued to consume a gluten containing diet and 0.5mg folic acid/d from supplements for 4 months and homocysteiene decreased to 12.1 mmol/L. Hyperhomocysteinaemia - a cardiovascular and obstetrical risk factor - might be a significant problem for patients with celiac disease on gluten-containing diet.

[Cancer in children with celiac disease. Gluten-sensitive enteropathy in a boy operated for Wilms tumour]. / Wystepowanie nowotworów zlosliwych u dzieci z celiakia. Enteropatia glutenowrazliwa u chlopca po zabiegu operacyjnym usuniecia guza Wilmsa.

In adults untreated coeliac disease (CD) is associated with a wide variety of malignant complications. The overall mortality in CD is approximately twice that of the general population. The excess deaths are due mainly to intestinal lymphoma. In Europe, only 26 cases of CD and cancer in children have been published. There is evidence that cancer and CD in children are underreported. We report a case of Wilms tumour in a child who developed CD. As a neonate the boy had been successfully operated for congenital mesoblastic nephroma. Gluten was introduced in his diet at age of 12 months. He developed vomiting, abdominal distention ad hypertransaminosaemia. Up to the age of 16 months he had lost 1500 g and coeliac crisis was diagnosed (IgAEMA titre 1:50 and in the duodenal biopsy specimen there was crypt hyperplastic total villous atrophy). Symptoms improved rapidly when gluten-free diet was initiated, and 4 years later, clinical and serological findings were normal. Wilms tumour accounts for 6% to 7% of all childhood malignancies. There are no reports in MEDLINE about coeliac disease in patients who have been operated for the tumour. This seemed intriguing because prevalence of gluten-sensitive enteropathy calculated for Europe varies between 1/100 and 1/300.