Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia - effect on median Phe/Tyr ratios.

BACKGROUND: Phenylalanine hydroxylase deficiency causes various degrees of hyperphenylalaninemia (HPA). Tetrahydrobiopterin (BH4; sapropterin) reduces phenylalanine (Phe) levels in responders, enabling relaxation of dietary therapy. We aimed to assess long-term effects of BH4 treatment in HPA patients. METHODS: Nine pre-pubertal BH4 responsive children were treated with BH4 for at least 2 years. The median dietary tolerance to Phe and levels of blood Phe, tyrosine (Tyr), zinc, selenium and vitamin B12 and anthropometric measurements, in the 2 years periods before and after the introduction of BH4 treatment were analyzed and compared. Adverse effects of BH4 were assessed. RESULTS: The daily Phe tolerance had tripled, from pretreatment median value of 620 mg (IQR 400-700 mg) to 2000 (IQR 1000-2000 mg) after 2 years of follow up (p<0.001). The median blood Phe levels during the 2 years period before introducing BH4 did not change significantly during the 2 years on therapy (from 200 µmol/L; IQR 191-302 to 190 µmol/L; IQR 135-285 µmol/L), but the median blood Phe/Tyr ratio had lowered significantly from pre-treatment value 4.7 to 2.4 during the 2 years on therapy (p=0.01). Median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change while on BH4 therapy (p=NS). No adverse effects were noticed. CONCLUSIONS: BH4 therapy enabled patients much higher dietary Phe intakes, with no noticeable adverse effects. Median blood Phe and Tyr levels, median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change significantly on BH4 therapy, but median Phe/Tyr ratios had lowered.

Dietary intake of macro- and micronutrients in Slovenian adolescents: comparison with reference values.

BACKGROUND: Data on a nationally representative dietary intake in Central Europe is lacking. We investigated the diet of adolescents in Slovenia. METHODS: Dietary habits were assessed using a food frequency questionnaire (n = 2,661), and present nutrition was assessed using a 3-day weighted dietary protocol (n = 197) for validation purposes. Dietary intake was calculated and compared with Central European [German (D), Austrian (A), and Swiss (CH); D-A-CH] recommendations and World Health Organization/Food and Agriculture Organization (WHO/FAO) recommendations. RESULTS: Adolescents consumed exceeding reference intake values of free sugars (boys 16% of energy, girls 17%), saturated fatty acids (SFA; 13% of energy), and sodium (boys 203%, girls 210% of the WHO/FAO upper limit), but below-reference intake values of polyunsaturated fatty acids (PUFA; boys 5% of energy; girls 6%), water (boys 1,786 ml/day, girls 2,016 ml/day), and fiber density (only girls 2.8 g/MJ, p < 0.001). Among micronutrients, below-reference intakes (% of D-A-CH: boys and girls, respectively, p < 0.05) were reported for folate (64 and 69%), fluoride (28 and 31%), and calcium (91 and 97%), as well as for vitamin D (20 and 20%). CONCLUSIONS: The dietary habits of Slovenian adolescents are less than optimal. They are characterized by exceeding reference intake values of free sugars, salt, and SFA, and a below-reference intake of PUFA, water, and several micronutrients.

Assessment of tetrahydrobiopterin (BH(4))-responsiveness and spontaneous phenylalanine reduction in a phenylalanine hydroxylase deficiency population.

A BH(4) loading test was performed in 36 patients from 34 unrelated families. The patients had 29 different genotypes, and previous data on only eight of them were found in the BIOPKU database. Thirteen patients were classified as classic PKU (35.1%), 14 as mild PKU (37.8%) and 9 as MHP (27.0%). Blood Phe levels were shown to reach a plateau after three full days of increased natural protein ingestion. Measuring the 24-hour blood Phe levels (T(-24), T(-16), T(0)) on the fourth day of increased protein ingestion before BH(4) administration showed that within 24h Phe on average increased by 2.4% in MHP patients, decreased by 2.7% in mild PKU patients and increased by 9.7% in classic PKU patients (NS for all comparisons); Phe only slightly decreased in responders by 0.2% but increased in non-responders by 7.8% (P>0.05). Altogether, 16 of 36 (44.4%) patients represented by 12 of 29 (41.4%) different genotypes were proven to be BH(4) responders, and four (10.8%) were slow-responders. Responders were 6/9 (66.7%) MHP patients, 10/14 (71.4%) mild PKU patients and 0/13 classic PKU patients. Twenty of the 29 (68.9%) genotypes harbored at least one mutation with a known PRA of 10% or more but only 11 (55%) of them were BH(4)-responsive. Spontaneous reduction of blood Phe levels within 24h on the fourth day of natural protein loading was observed only in mild PKU patients and was shown not to be an important part of the BH(4)-response. 73.3% of genotypes containing at least one allele with a PRA of at least 30% were found to be BH(4) responsive; a PRA of at least 15.5% was needed for the responder genotype in our population.

Under- and over-reporting of energy intake in slovenian adolescents.

OBJECTIVE: To examine under- and over-reporting of energy intake (EI) among adolescents and to compare relative food and nutrient intakes of under-reporters (UR), over-reporters (OR), and the whole population to acceptable reporters (AR). DESIGN: All adolescents completed food frequency questionnaires at regional health centers, and a subgroup also completed a 3-day weighed dietary protocol at home. SETTING: This study is a part of the first national representative study on dietary habits of Slovenian adolescents. PARTICIPANTS: In total, 2,813 adolescents entering high school (10% of the population); participation rate was 95%. MAIN OUTCOME MEASURES: Absolute EI and relative intakes of food and nutrients. ANALYSIS: Prodi (version 5.2 expert plus, Nutri-Science, Stuttgart, Germany, 2004) software was used to evaluate dietary intakes; t test, analysis of variance, and Mann-Whitney testing were used for differences between means, and chi-square was used for differences between proportions. Level of significance was set at P = .05. RESULTS: The prevalence of UR and OR was 34% and 10% among boys, and 27% and 11% among girls. Under-reporters reported lower energy percentage from carbohydrates, higher energy percentage from fats and proteins, and higher micronutrient densities than AR. CONCLUSIONS AND IMPLICATIONS: Under-reporting and over-reporting are widespread among Slovenian adolescents. Exclusion of UR and OR does not influence mean value of EI when assessing the diet of a group as a whole.

Food intake in Slovenian adolescents and adherence to the Optimized Mixed Diet: a nationally representative study.

OBJECTIVES: To investigate the food intake of Slovenian adolescents and to compare it with food-based dietary guidelines developed for children and adolescents, named the Optimized Mixed Diet (OMD). The OMD is a useful tool for the evaluation of food intake of adolescents. DESIGN: All adolescents completed an FFQ at a regional health centre; a subgroup also completed a 3 d weighed dietary protocol at home. SETTING: This study is a part of the first national representative study on the dietary habits of Slovenian adolescents. SUBJECTS: This cross-sectional study included a representative sample of 2813 Slovenian adolescents entering high school, aged 14-17 years, from all ten geographical regions of Slovenia. RESULTS: The greatest deviations from the recommended intakes of the main food groups in the OMD were significantly lower intakes of (P < 0·001, mean): vegetables (179 and 163 g/d in boys and girls, respectively), bread/cereals (271 and 226 g/d), potatoes/rice/pasta (212 and 163 g/d); in boys also a significantly lower intake of fruits (mean: 321 g/d, P < 0·001) and a significantly higher intake of meat/meat products (mean: 126 g/d, P < 0·001). Additionally, the results show too high intake of sugar-sweetened beverages and too low intakes of fish and plant oils in both genders. CONCLUSIONS: The food intake pattern of Slovenian adolescents deviates markedly from a healthy eating pattern. Nutrition education and interventions are needed for Slovenian adolescents.

Adequate iodine intake of Slovenian adolescents is primarily attributed to excessive salt intake.

In Slovenia, table salt iodization has been applied to combat iodine deficiency. Recently, we found that Slovenian adolescents attained iodine sufficiency (median urinary iodine concentration was 140 microg/L; prevalence of goiter was <1%). National data indicate that salt intake of Slovenian population is too high (150% above the recommended limit); therefore, we hypothesized that sufficient iodine intake in adolescents can be primarily attributed to excessive salt intake. In a cross-sectional study, we investigated iodine and salt intake in Slovenian adolescents as well as the contributions of different foods to their intake. We determined the iodine and salt intake of a national representative sample of 2581 adolescents, aged 14 to 17 years, using the Food Frequency Questionnaire (FFQ). The FFQ covered habitual diets over the past year, and 2485 (96%) adolescents completed a valid FFQ (1370 girls, 1115 boys). The iodine intake was 189.7 +/- 2.6 microg/d (mean +/- standard error of mean), well above the recommended 150 microg/d (P < .001). Table salt was by far the biggest dietary source of iodine and sodium for both sexes. Total salt intake (mean +/- standard error of mean, 10.4 +/- 0.2 g/d) significantly exceeded the upper World Health Organization limit (<5 g/d, P < .001), especially in boys (11.5 +/- 0.3 vs 9.4 +/- 0.2 g/d in girls, P < .001). The main food sources of salt were table salt (33%), bread (24%), salty snack products (10%), meat products (8%), fish products (6%), and milk (4%). Salt intake from foods, excluding table salt, was 6.9 g/d (67% of total salt intake). We conclude that although Slovenian adolescents are iodine sufficient, their salt intake, especially among boys, is too high. Several nutritional interventions are proposed to reduce total salt intake while ensuring adequate iodine intake.