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Abstract: We report citrin deficiency in a neonatal non-East-Asian patient, the ninth Caucasian reported with this disease. The association of intrahepatic cholestasis, galactosuria, very high alpha-fetoprotein and increased plasma and urine citrulline, tyrosine, methionine and threonine levels suggested citrin deficiency. Identification of a protein-truncating mutation (c.1078C>T; p.Arg360*) in the SLC25A13 gene confirmed the diagnosis. An immediate response to a high-protein, lactose-free, low-carbohydrate formula was observed. Our report illustrates the need for awareness on citrin deficiency in Western countries. [Copyright &y& Elsevier]

• Children show a biased initial visual orienting towards food cues regardless of their weight. • Overweight children engage and maintain attention at food cues. • Attention processing of food cues differs between healthy and overweight children. • An attentional bias to food is showed in high-risk children for adult obesity. Overweight during childhood constitutes a high-risk factor for adult obesity. An abnormal attention to food stimuli (i.e., a bias) has been suggested as an underlying mechanism to the onset and/or maintenance of obesity. Previous literature supports the existence of a biased attention toward food stimuli in adults with obesity. However, it is unknown whether this attentional bias occurs in high-risk children for adult obesity. We aimed to examine attentional biases to food at different stages of attention processing in overweight children. A dot-probe task was applied to 25 children with overweight and 25 healthy-weight children (8–12 years old). Attentional preference to or avoidance of pleasant food stimuli, which were displayed simultaneously with pleasant non-food stimuli (matched in valence and arousal), was examined at 100-ms (initial visual orienting), 500-ms (attention engagement), and 1500-ms (maintained attention) presentation rates. Both children with overweight and healthy-weight children showed an attentional bias toward food images at a 100-ms presentation rate. However, unlike healthy-weight children, those with overweight showed an attentional preference toward food images at 500- and 1500-ms presentation rates. A biased initial orienting to food cues can be found regardless of weight. However, a biased attention engagement and a biased maintained attention toward food cues are characteristics of children with overweight. Therefore, as in adults, children at risk of adult obesity have an abnormal attentional processing of food stimuli. [ABSTRACT FROM AUTHOR]

Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) treated patients, who should receive optimal supplementation although this is not yet fully established. We conducted a cross-sectional observational multicenter study including 156 patients with hyperphenylalaninemia. Patients were stratified by age, phenotype, disease detection and type of treatment. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, and biochemical parameters (total protein, prealbumin, electrolytes, selenium, zinc, B 12 , folic acid, ferritin, 25-OH vitamin D) were collected in all patients. 81.4% of patients had biochemical markers out of recommended range but no clinical symptoms. Total protein, calcium, phosphorus, B 12 , ferritin, and zinc levels were normal in most patients. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18 years old), showing almost all (96.3%) an adequate adherence to diet. Selenium was diminished in 25% of patients (95% with PKU phenotype) and also 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B 12 levels were found diminished in patients with low adherence to diet. Patients under BH4 therapy only showed significant lower levels of B 12 . This study shows a high percentage of prealbumin and selenium deficiencies as well as an increased level of folic acid in PKU treated patients, which should lead us to assess an adjustment for standards supplements formulated milks. [ABSTRACT FROM AUTHOR]

Background and Aims Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0–4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. Methods We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH 4 responsiveness and growth outcome. Results No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial = − 0.57 ± 1.54; final = − 0.52 ± 1.29; BMI Z-score: initial = 0.17 ± 1.05; final = 0.18 ± 1.00) or the diet-only group (height Z-score: initial = − 0.92 ± 0.96; final = − 0.78 ± 1.08; BMI Z-score: initial = 0.17 ± 0.97; final = − 0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences ( p > 0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6–60.3] to 56.5 [39.8–68.3] mg kg − 1 day − 1 ) and natural protein intake (from 1.0 [0.8–1.7] to 1.5 [1.0–1.8] g kg − 1 day − 1 ), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p < 0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. Conclusions Our study indicates that treating 0–4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Treatment of phenylketonuria based upon strict vegetarian diets, with very low phenylalanine intake and supplemented by phenylalanine-free formula, has proven to be effective in preventing the development of long-term neurological sequelae due to phenylalanine accumulation. On the other hand, such diets have occasionally been reported to hinder normal development, some individuals presenting with growth retardation. Tetrahydrobiopterin therapy has opened up new treatment options for a significant proportion of phenylketonuric patients, enabling them to eat normal diets and be freed from the need to take synthetic supplements. However, little is known about how this therapy affects their physical development. Methods: We conducted a retrospective longitudinal study examining anthropometric characteristics (height, weight, body mass index and growth speed Z-scores) in a cohort of phenylketonuric patients on tetrahydrobiopterin therapy (38 subjects) comparing their characteristics with those of a group of phenylketonuric patients on phenylalanine-restricted diets (76 subjects). Nutritional issues were also considered, to further explore the possibility of higher natural protein intake being associated with better physical development. Data were collected every six months over two different periods of time (two or five years). Results: No improvement was observed in the aforementioned anthropometric variables in the cohort on tetrahydrobiopterin therapy, from prior to starting treatment to when they had been taking the drug for two or five years. Rather, in almost all cases there was a fall in the mean Z-score for the variables during these periods, although the changes were not significant in any case. Further, we found no statistically differences between the two groups at any considered time point. Growth impairment was also noted in the phenylketonuric patients on low-phenylalanine diets. Individuals on tetrahydrobiopterin therapy increased their natural protein intake and, in some instances, this treatment enabled individuals to eat normal diets, with protein intake meeting RDAs. No association was found, however, between higher protein intake and growth. Conclusion: Our study identified growth impairment in patients with phenylketonuria on tetrahydrobiopterin, despite higher intakes of natural proteins. In fact, individuals undergoing long-term tetrahydrobiopterin treatment seemed to achieve similar developmental outcomes to those attained by individuals on more restricted diets. [Copyright &y& Elsevier]