Management precautions for risk of obesity are necessary among infants with PKU carrying the rs113883650 variant of the LAT1 gene: A cross-sectional study.

Patients with phenylketonuria (PKU), an inborn error of phenylalanine metabolism, require consistent treatment to avoid the brain toxicity caused by hyperphenylalaninemia. The treatment consists of life-long use of a low-phenylalanine diet, which aims at decreasing hyperphenylalaninemia and maintaining blood phenylalanine concentration in a safe range. Problems with balancing diet can result in suboptimal treatment outcomes; however, recent findings suggest that genetic alteration of the transport of phenylalanine might result in an additional health burden. We assessed the effect of a common variant (rs113883650) of the LAT1(SLC7A5) gene, which encodes the main transmembrane phenylalanine transporter, on the development of overweight in 54 infants with PKU who received standard therapy and adhered well to therapeutic prescriptions, and in 55 infants with a milder disease form-the so-called mild hyperphenylalaninemia (MHP), which does not require treatment. We found that infants with PKU-carriers of the rs113883650 variant had significantly higher Body Mass Index (BMI) at 1 year compared to PKU infants without the variant (mean BMI Z-Score of +1.15 SD vs -0.15 SD, respectively; t(52) = 5.25, p = 0.00005). Conversely, no significant BMI differences were detected in the subgroups of infants with MHP (t(53) = 1.15, p = 0.25). Additionally, high BMI in infants with PKU-carriers of the rs113883650 variant positively correlated with high variability of their blood phenylalanine levels (r(52) = 0.42, p = 0.002). It should be noted that this is an observational study, which does not determine causation. Nevertheless, our findings show that the rs113883650 variant of the LAT1 gene may be a risk factor for overweight in properly treated infants with PKU. Management precautions should be taken to prevent the development of overweight and obesity.

Mental distress of parents with chronic diseases during the COVID-19 pandemic in Australia: A prospective cohort study.

OBJECTIVE: To-date there has been limited examination of the experience of the COVID-19 pandemic in parents who suffer from chronic physical conditions. We aimed to 1) examine whether presence of a chronic disease predicts differential latent distress profile memberships, and 2) assess factors that could predict different distress profiles in the sub-group of parents with a chronic disease. METHODS: We used a sample of 1618 parents, from the longitudinal COVID-19 Pandemic Adjustment Study, who completed a measure of mental distress (Depression, Anxiety and Stress Scale) at 13 data collection points. Distress profiles were assessed with the latent profile analysis. RESULTS: We identified four distinct mental distress profile memberships, with the most common membership characterised by very low (48.1%), followed by low (31.9%), moderate (15.7%), and high (4.3%) distress scores. A higher proportion of parents with chronic diseases belonged to profiles experiencing low (34.7% vs. 30.4%), moderate (18.7% vs. 14.1%), and high (5.5% vs. 3.7%) compared to very low (41.2% vs. 51.8%) distress levels than other parents. Residing in Victoria, younger age, lower levels of social support and appraisal of COVID as risk were associated with membership to higher compared to very low distress profiles. CONCLUSION: Our findings highlight the importance of considering chronic disease co-morbidity as an additive risk factor in addressing mental health outcomes of parents during pandemic-like events, since parents with chronic conditions are more vulnerable to experiencing worse mental distress. Future interventions should focus on ways to strengthen social support and provide guidance for managing threat appraisal.

The rs113883650 variant of SLC7A5 (LAT1) gene may alter brain phenylalanine content in PKU.

Functional alteration of the LAT1 amino acid transporter may be responsible for interindividual differences in cerebral phenylalanine content and the lack of intellectual disability in some patients with untreated phenylketonuria. We assessed the effect of the common variant rs113883650 of the SLC7A5 (LAT1) gene on brain phenylalanine content, as measured with use of magnetic resonance spectroscopy. Our results suggest that the presence of this variant could influence the amount of phenylalanine in the brain.

Carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene increases the risk of obesity in infants with phenylketonuria.

PURPOSE: Phenylketonuria (PKU) can be effectively treated with the use of a low-phenylalanine diet. However, some patients become overweight despite proper dietary treatment. We hypothesized that this phenomenon could be explained by the presence of specific variants within the genes involved in phenylalanine transport or in the phenylalanine transamination/oxygenation pathway. METHODS: We selected a clinically homogenous group of 100 infants with PKU and assessed their growth patterns in the context of dietary phenylalanine tolerance. Next, within the sample, we performed exome sequencing and assessed a potential relationship between the observed phenotypical variability and the presence of structural variants in a priori selected genes of interest. RESULTS: We detected a highly significant association between overweight and carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene, which encodes the main transmembrane transporter of large neutral amino acids and of thyroid hormones. CONCLUSIONS: Our findings suggest a pharmacogenetic effect of the relatively common rs113883650/rs2287120 haplotype of the SLC7A5 gene. This can have practical implications for patients with PKU, since treatment protocols need to be reassessed to better prevent overweight in the carriers of the above variant.