Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children are correlated with dietary compliance.

Phenylketonurics display lower arachidonic acid levels in plasma lipids, reflecting the lower intake due to the dietary treatment poor in phenylalanine-rich animal foods. Plasma arachidonic acid levels and serum thromboxane B2 concentrations have been measured in 13 treated phenylketonuric children and compared with those of 12 healthy controls. A direct relationship between plasma arachidonic acid and thromboxane B2 concentrations has been observed only in phenylketonurics, whose plasma arachidonic acid status correlated negatively with their dietary compliance. These results suggest that the low consumption of animal fats may contribute to modulate the production of arachidonic acid-derived platelet eicosanoids.

Fatty acid metabolism in phenylketonuria.

Children treated for phenylketonuria (PKU) have a low intake of whole animal foods. Consequently, the dietary intake of long-chain polyunsaturated fatty acids (PUFA) is just a few milligrams per day, mostly represented by arachidonic acid (AA). In a consecutive series of studies, we assessed in treated PKU children their long-chain PUFA status, the AA-related eicosanoid synthesis and the effects of specific PUFA supplementations. We found that the good compliance with the dietary regimen negatively influences the long-chain PUFA status and serum eicosanoid release from platelets. Supplementation with either marine or blackcurrant oils modifies the long-chain PUFA status of PKU children without approaching the fatty acid pattern of a healthy control population. Good-compliant PKU patients have diet-related, low levels of circulating long-chain PUFA, whose clinical and functional consequences deserve further investigation. The effects of dietary supplementations with long-chain PUFA of both the n-6 and n-3 series should be carefully evaluated.

Preliminary results of a nutritional survey in a sample of 35,000 Italian schoolchildren.

An investigation of the nutrient intake of a large-scale sample (n = 35,072), drawn from the Italian school-age population (7-10 years) was carried out in a nationwide survey of nutritional patterns. Friuli, the Piedmont, Latium and Sicily regions were selected as representative of the nation's north-south and east-west socio-economic divisions. A food frequency questionnaire was used to assess nutritional intake. Traditional methods of 24-h dietary recall and a weighted food diary were used in subsamples to assess the validity of the food frequency questionnaire. Our data suggest that the average diet of Italian schoolchildren is rich in protein (especially animal proteins) and lipids (prevalently saturated fatty acids), but that carbohydrate and fibre intakes remain generally low. The relatively low calcium intake among girls and a widespread, more than adequate iron intake are also noteworthy. The food and nutrient intakes assessed suggest a dietary pattern with several positive points, but also reveal potential hazards for a wider population spectrum. The type of large-scale nutritional monitoring with a multi-method approach can be used in Italy and elsewhere to describe the dietary trends of a school-age population.

PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population.

The results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

Early breastfeeding is linked to higher intelligence quotient scores in dietary treated phenylketonuric children.

Strict control of phenylalanine intake is the main dietary intervention for phenylketonuric children. Whether other dietary-related factors improve the clinical outcome for treated phenylketonuric children in neurodevelopmental terms, however, remains unexplored. We retrospectively compared the intelligence quotient (IQ) score of 26 school-age phenylketonuric children who were either breastfed or formula fed for 20-40 days prior to dietary intervention. Children who had been breastfed as infants scored significantly better (IQ advantage of 14.0 points, p = 0.01) than children who had been formula fed. A 12.9 point advantage persisted also after adjusting for social and maternal education status (p = 0.02). In this sample of early treated term infants with phenylketonuria there was no associated between IQ scores and the age at treatment onset and plasma phenylalanine levels during treatment. We conclude that breastfeeding in the prediagnostic stage may help treated infants and children with phenylketonuria to improve neurodevelopmental performance.

The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children.

Dietary-treated phenylketonuric patients (PKUs) display low levels of long-chain polyunsaturated fatty acids (PUFA) in plasma lipids. In a 6-month clinical trial we observed a decrease of triglycerides and an increase of n-3 long-chain PUFA in plasma of PKUs supplemented with fish oil, while no major differences in respect to the baseline values were found in a group supplemented with blackcurrant oil. A more complete source of long-chain PUFA of both the n-6 and n-3 series should be investigated for dietary supplementation of PKU patients.

Nutrition in children affected by inherited metabolic diseases.

Diet-therapy represents an elective approach to the treatment of several inborn errors of metabolism. According to the type of disease, dietary intervention can be addressed to three different goals: a) dietary restriction (global or partial) of one or more nutritional components become "toxic" because of the occurring enzymatic defect; b) supplementation with a given defective nutritional component; c) elimination through the use of diet and drugs of the accumulated "toxic" compounds. These interventions are aimed at overtaking the metabolic block and to avoid the accumulation of intermediate "toxic" substrates. The efficacy of the therapy should then be evaluated by means of a thorough biochemical and clinical follow-up (including anthropometric and psychomotor development parameters). In particular, nutritional indexes should be constantly monitored in order to support the dietary therapy, discover and correct any possible nutritional deficiency secondary to the "by exclusion dietary regimen". To elucidate these general principles, we discuss in detail some hereditary diseases of amino acid (phenylketonuria) and carbohydrate (glycogen storage disease and galactosemia) metabolism that, being responsive to the nutritional intervention, can be considered reliable examples of all the problems linked to diagnosis, acute and long-term therapy and follow-up of these diseases.

Lipid status and fatty acid metabolism in phenylketonuria.

Owing to dietary treatment, patients with phenylketonuria (PKU) are supplied with only small amounts of animal fats and show low blood cholesterol levels and a poor long-chain polyunsaturated fatty acid (LC-PUFA) status. Endogenous synthesis should compensate for the physiological need for cholesterol for growth, but supplementary exogenous LC-PUFA seems advisable. PKU infants could develop depletion of docosahexaenoic acid, fundamental for the functional development of the central nervous system. The availability of arachidonic acid from plasma in PKU has been found to be related to dietary compliance, and seems to influence the synthesis of arachidonate-derived eicosanoids. Trials of dietary supplementation of PKU patients with oils containing LC-PUFA are in progress, but the functional consequences of these supplementations need further investigation.

Effects of diet on the lipid and fatty acid status of full-term infants at 4 months.

OBJECTIVE: To compare the effects of the exogenous supply of long-chain polyunsaturated fatty acids (LCP) and cholesterol on the lipid and fatty acid status in full-term, 4-month old infants. METHODS: Twenty-three infants received a standard infant formula while twenty-one were given a formula enriched with LCP and cholesterol in a prospective, randomized study. The composition of the two formulas differed only in fat quality. A group of fifteen breastfed infants fed was used as reference. No one was complemented with solid foods before blood sampling at 4 months of life. RESULTS: Differences in total-cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels between feeding groups were mainly gender-related. Dietary cholesterol tended to increase LDL-C plasma levels. The breastfed and the enriched formula-fed groups had higher levels of circulating LCP than the group that received the standard formula. In the erythrocytes of infants fed the standard formula, C22:6 n-3 levels were less than 50% those of the breastfed and the enriched formula-fed ones. Higher C20:4 n-6 levels were found in the erythrocytes of the enriched formula-fed group. CONCLUSIONS: Formula-fed, full-term infants maintain a lipid and fatty acid status close to that of breastfed infants when supplied with dietary LCP and cholesterol.

PKU-related dysgammaglobulinaemia: the effect of diet therapy on IgE and allergic sensitization.

The effect of diet on the development of immunoallergic signs and symptoms in children with phenylketonuria (PKU) was evaluated. Immunological indices of 58 children with PKU treated with diets were compared to the immunological indices of 58 healthy (non-PKU) children. In the PKU group, 39 children had been placed on diet therapy within the first month of life; 19 children had been placed on diet therapy after 6 months of age. Total circulating lymphocytes; CD3+, CD4+, CD8+ circulating lymphocytes; and serum IgA, IgM, IgG and total IgE levels were measured for each child. Skin prick tests were performed for common inhalant and food allergens. Every 3 months over the 2-year period of this study, the signs and symptoms of eczema, allergic rhinitis and asthma were recorded. The PKU group had lower IgG levels (p = 0.004) and higher total IgE levels (p = 0.0001) than the control group. Significantly lower IgE levels were found in children started on diet therapy within the first month of life compared with those started on diet therapy after 6 months of age (p = 0.0001). Allergic sensitization was significantly more frequent in the PKU group (24/58 vs 13/58, z = 2.00, p < 0.05), but no significant difference in the incidence of eczema and allergic rhinitis was found. Asthma was less frequent in the PKU group than in the control group (5/58 vs 14/58, z = 2.09, p < 0.05). Thus, diet appeared to prevent the development of immunoallergic signs and symptoms.

[Thyroid function in children with Down's syndrome]. / La funzionalità tiroidea in bambini affetti da sindrome di Down.

The aim of the present study was to evaluate thyroid function in 45 Down's syndrome patients in order to verify the hypothesis of an increased risk of thyroid disorders associated with trisomy 21. A patient with subclinical hypothyroidism (TSH 16.6 microU/ml; T4 6.4 micrograms/dl) was diagnosed in a group of 28 subjects with Down's syndrome studied at a mean age of 6 years and 5 months using T3, T4, FT3, FT4, TSH assays and clinical examination. T4 and TSH values were also measured in 10 of these children at the neonatal screening. One infant presented transient neonatal hyperthyrotropinemia but later became euthyroid. The analysis of thyroid hormone values at the neonatal screening of other 17 subjects with Down's syndrome did not reveal other cases with thyroid function disorders. The results of this study highlight that altered thyroid functions are evident in children with trisomy 21 associated with heart anomalies. A careful clinico-endocrinological follow-up of patients with Down's syndrome is recommended in order to ensure an early diagnosis of thyroid function disorders and/or autoimmune diseases which might complicate the evolution of trisomy and negatively affect outcome.