Acute intoxication‐type inborn errors of metabolism (IT‐IEM) such as urea cycle disorders and non‐acute IT‐IEM such as phenylketonuria have a major impact on paediatric patients' life. Patients have to adhere to a strict diet but may face neurocognitive impairment and – in acute diseases – metabolic decompensations nevertheless. Research on the subjective burden of IT‐IEM remains sparse. Studies with appropriate sample sizes are needed to make valid statements about health‐related quality of life (HrQoL) in children and adolescents with IT‐IEM. Six international metabolic centres contributed self‐reports and proxy reports of HrQoL (assessed with the Paediatric Quality of Life Inventory) to the final data set (n = 251 patients; age range 2.3‐18.8 years). To compare HrQoL of the patient sample with norm data and between acute and non‐acute IT‐IEM, t tests were conducted. To examine the influence of child age, sex, diagnosis and current dietary treatment on HrQoL, multiple linear regression analyses were conducted. Self‐reports and proxy reporst showed significantly lower HrQoL total scores for children with IT‐IEM compared to healthy children. Current dietary treatment significantly predicted lower proxy reported total HrQoL. Children with non‐acute IT‐IEM reported significantly lower psychosocial health and emotional functioning than children with acute IT‐IEM. The patient sample showed significantly impaired HrQoL and a diet regimen remains a risk factor for lower HrQoL. Differences in HrQoL between acute and non‐acute IT‐IEM subgroups indicate that factors beyond symptom severity determine the perception of disease burden. Identifying these factors is of crucial importance to develop and implement appropriate interventions for those in need.

Objective: To analyze trends in risk and protective factors for non-communicable diseases (NCD) and access to preventive tests in the population with health insurance in Brazilian state capitals between 2008 and 2015. Methods: This is a cross-sectional study that analyzed data collected from the Surveillance of Risk and Protective Factors for non-communicable diseases (NCD) Telephone Survey (Sistema Nacional de Vigilância de Doenças Crônicas por Inquérito Telefônico -Vigitel) on adults aged 18 years and older. We analyzed trends in NCD indicators among health insurance users in approximately 30 thousand interviews done between 2008 and 2015. We used the simple linear regression model to calculate the trends. Results: Health insurance users showed an increase in the prevalence of protective factors such as fruit and vegetable consumption, and physical activity in leisure time. Also, there was a decrease in risk factors such as smoking and soft drink consumption, increase in mammography coverage, and a drop in smoking prevalence. However, overweight, obesity, and diabetes increased. Conclusion: There are differences according to gender, and, in general, women accumulate more protective factors and men, more risk factors.

Early dietary treatment of phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, results in normal cognitive development. Although health-related quality of life (HRQoL) of PKU patients has been reported as unaffected in high-income countries, there are scarce data concerning HRQoL and adherence to treatment of PKU children and adolescents from Brazil. The present study compared HRQoL scores in core dimensions of Brazilian early-treated PKU pediatric patients with those of a reference population, and explored possible relationships between adherence to treatment and HRQoL. Early-treated PKU pediatric patient HRQoL was evaluated by self- and parent-proxy reports of the Pediatric Quality of Life Inventory (PedsQL) core scales. Adherence to treatment was evaluated by median Phe levels and percentage of results within the therapeutic target range in two periods. Means for total and core scales scores of PedsQL self- and parent proxy-reports of PKU patients were significantly lower than their respective means for controls. Adequacy of median Phe concentrations and the mean percentage of values in the target range fell substantially from the first year of life to the last year of this study. There was no significant difference in mean total and core scale scores for self- and parent proxy-reports between patients with adequate and those with inadequate median Phe concentrations. The harmful consequences for intellectual capacity caused by poor adherence to dietary treatment could explain the observed decrease in all HRQoL scales, especially in school functioning. Healthcare system and financial difficulties may also have influenced negatively all HRQoL dimensions.

BackgroundPhenylketonuria (PKU) is an autosomal recessive disease resulting from mutations in the PAH gene. Most of the patients are compound heterozygotes, and genotype is a major factor in determining the phenotypic variability of PKU. More than 1,000 variants have been described in the PAH gene. Rio de Janeiro's population has a predominance of Iberian, followed by African and Amerindian ancestries. It is expected that most PKU variants in this Brazilian state have originated in the Iberian Peninsula. However, rare European, African or pathogenic variants that are characteristic of the admixed population of the state might also be found.MethodsA total of 102 patients were included in this study. Genomic DNA was isolated from dried blood spots. Sanger sequencing was used for PAH gene variant identification. Deletions and duplications were also screened using MLPA analysis. Haplotypes were also determined.ResultsNine (8.8%) homozygous and 93 (91.2%) compound heterozygous patients were found. The spectrum included 37 causative mutations. Missense, nonsense, and splicing pathogenic variants corresponded to 63.7%, 2.9%, and 22.6% of the mutant alleles, respectively. Large (1.5%), and small deletions, inframe (5.4%) and with frameshift (3.9%), comprised the remainder. The most frequent pathogenic variants were: p.V388M (12.7%), p.R261Q (11.8%), IVS10‐11G>A (10.3%), IVS2+5G>C (6.4%), p.S349P (6.4%), p.R252W (5.4%), p.I65T (4.4%), p.T323del (4.4%), and p.P281L (3.4%). One novel variant was detected: c.934G>T (p.G312C) [rs763115697].ConclusionThe three most frequent pathogenic variants in our study (34.8% of the alleles) were also the most common in other Brazilian states, Portugal, and Spain (p.V388M, p.R261Q, IVS10‐11G>A), corroborating that the Iberian Peninsula is the major source of PAH mutations in Rio de Janeiro. Pathogenic variants that have other geographical origins, such IVS2+5G>C, p.G352Vfs*48, and IVS12+1G>A were also detected. Genetic drift and founder effect may have also played a role in the mutation spectrum we observed.