Blood phenylalanine instability strongly correlates with anxiety in phenylketonuria

We assessed the relationship between anxiety and long-term metabolic control in adolescents with phenylketonuria (PKU). We used a standardized psychological test to measure anxiety level and analyzed lifelong blood phenylalanine stability in a selected group of 25 PKU teenagers with treatment adherence problems. We demonstrated significant correlations of anxiety with variability of blood phenylalanine concentrations and with severity of hyperphenylalaninemia. Avoiding blood phenylalanine fluctuations in childhood can probably reduce anxiety in PKU adolescents

Dynamics of hyperphenylalaninemia and intellectual outcome in teenagers with phenylketonuria

Insufficient treatment adherence after early childhood is frequently observed in patients with phenylketonuria. Assessment of these individuals' long-term metabolic control could enable early detection of the risk of intellectual deterioration resulting from high blood phenylalanine concentration. However, the predictive value of specific parameters related to individual dynamics of hyperphenylalaninemia is not clear. Here, we assessed the impact of blood phenylalanine fluctuations during the first 12 years of life on cognitive outcome in early and continuously treated teenagers with phenylketonuria. We have analyzed a total of 5141 results of blood phenylalanine measurements in 32 patients. The phenylalanine levels of these patients were usually acceptable during their early childhood, but the control of hyperphenylalaninemia worsened and the average treatment adherence dropped to 40% during the late primary school. Our analysis revealed a strong association between the Wechsler intelligence verbal scores and the mean of the yearly means of phenylalanine concentrations (r=-0.62). The correlations of IQ scores with median phenylalanine concentrations and the variability of blood phenylalanine levels gave weaker associations. The Wechsler verbal scores were also strongly correlated with the treatment adherence level during preschool and late primary school (r=0.61 and 0.72). The mean of the yearly means of blood phenylalanine concentrations appears to be a better predictor of cognitive outcome in children with phenylketonuria than other parameters related to phenylalanine fluctuations. The percentage of acceptable phenylalanine levels below 50-60% should be regarded as a "red flag" due to the risk of intellectual deterioration in patients

MTRNR2L12 : a candidate blood marker of early Alzheimer's disease-like dementia in adults with Down Syndrome

Morphological abnormalities observed typically in the brains of adults with Down syndrome are identical with those present in patients with Alzheimer’s disease. However, only some adults with Down syndrome suffer from early dementia, whereas others remain unaffected. We aimed to identify the genomic background responsible for this observation. We performed cognitive assessment and genome expression analysis of blood mononuclear cells in seniors with Down syndrome. Unaffected elderly patients and younger patients with severe cognitive disability or cognitive deterioration differed significantly with regard to the MTRNR2L12 gene. Our findings suggest the potential value of this gene as a blood marker of early dementia in individuals with Down syndrome

Expression of SCGB1C1 gene as a potential marker of susceptibility to upper respiratory tract infections in elite athletes : a pilot study

High levels of exercise in athletes result in temporary immunosuppression, which could increase the susceptibility to upper respiratory tract infections. Understanding of immunological mechanisms responsible for this phenomenon could enable optimization of training schemes for elite athletes and avoidance of infection-related episodes of absence during sports championships. The aim of this study was to detect genes that may be responsible for modulation of individual susceptibility to infections. The blood and saliva samples were collected from 10 healthy, medically examined kayakers (4 females and 6 males) aged 24.7 ± 2.3 years. All samples were taken in the morning, after overnight fasting, in a seated position. The ELISA method was used to determine the levels of secretory immunoglobulin A (sIgA) and interleukin 5 (IL-5). Whole genome expression in blood was assessed using microarrays. The study did not reveal any significant correlation between genome expression and sIgA concentration. However, low expression of a gene involved in protection against the common cold – secretoglobin 1C1 (SCGB1C1) – was detected in athletes with high IL-5 concentrations (corrected p=0.00065; fold change=3.17). Our results suggest that blood expression of the SCGB1C1 gene might be a marker of susceptibility to upper respiratory tract infections in athletes

Ocena dynamiki mózgowego stężenia fenyloalaniny u pacjentów z fenyloketonurią

Background: Phenylketonuria (PKU) is the most common inborn error of metabolism in man. Brain phenylalanine kinetics can determine neurological treatment outcome in phenylketonuria. The aim of our study was to test a simplified magnetic resonance spectroscopy method for assessment of brain phenylalanine dynamics in PKU patients. Material/Methods: Brain phenylalanine concentration (measured by means of magnetic resonance spectroscopy) and blood phenylalanine concentrations changes occurring within 24 hours after oral phenylalanine loading were analyzed in 5 PKU patients. Results/Conclusions: The brain/blood phenylalanine ratio in 3 persons with normal intelligence was lower than in 2 with borderline intelligence or mild mental retardation. In our opinion the proposed method could be useful for assessment of brain phenylalanine dynamics in PKU patients

Cardiovascular anomalies among 1005 fetuses referred to invasive prenatal testing - a comprehensive cohort study of associated chromosomal aberrations

This retrospective cohort study comprehensively evaluates cardiovascular anomalies (CVAs) and associated extracardiac structural malformations (ECMs) among 1005 fetuses undergoing invasive prenatal testing at a single tertiary Polish center in the context of chromosomal aberrations detected in them by array comparative genomic hybridization (aCGH) and G-band karyotyping. The results of our study show that CVAs are among the most common malformations detected in fetuses undergoing invasive prenatal testing, as they affected 20% of all cases seen in our department. Septal defects predominated among fetuses with numerical aberrations, while conotruncal defects were the most common findings among fetuses with pathogenic copy number variants (CNVs). In 61% of cases, CVAs were associated with ECMs (the diagnosis was confirmed postnatally or in cases of pregnancy termination by means of autopsy). The most common ECMs were anomalies of the face and neck, followed by skeletal defects. In total, pathogenic chromosomal aberrations were found in 47.5% of CVAs cases, including 38.6% with numerical chromosomal aberrations. Pathogenic CNVs accounted for 14.5% of cases with CVAs and normal karyotype. Thus, our study highlights the importance of assessing the anatomy of the fetus, and of the genetic testing (preferably aCGH) that should be offered in all CVA and ECM cases

The amino acid profile in blood plasma of young boys with autism

The aim of the study: It has been suggested that some amino acids are involved in the pathogenesis of autistic disorders. The aim of the study was to evaluate the plasma amino acids profile in young males with autism. Method: Total of 27 autistic boys (aged 2–10 years, the study group) without any metabolic disorders and 13 healthy boys (aged 2–9 years, control group) were included in the study. In all subjects fasting blood plasma free amino acids (both exogenous and endogenous) were quantitatively measured by high performance liquid chromatography with UV-VIS detection. Results: The mean plasma concentration values of citrulline, α-aminobutyric acid, isoleucine, leucine, phenylalanine, tryptophan and ornithine were significantly lower in boys with autism as compared to the control group (p < 0.03, p < 0.04, p < 0.02, p < 0.02, p < 0.05, p < 0.02, p < 0.05, respectively). The areas under the Receiver Operating Characteristic curves for these amino acids ranged from 0.637 to 0.726. None of the amino acids measured differentiate autistic children from healthy children. The sum of exogenous amino acids was lower in the study group than in the control group but this difference was not statistically significant. Conclusions: Lower levels of exogenous amino acids confirm the possible role of these amino acids in autism. Determination of exogenous amino acids in plasma, however, cannot be used as a diagnostic test but it can still support autistic patients care

Development and maturation of the immune system in preterm neonates : results from a whole genome expression study

To expand the knowledge about the consecutive expression of genes involved in the immune system development in preterm neonates and to verify if the environment changes the gene expression after birth we conducted a prospective study that included three cohorts: (A) extremely (gestational age (GA): 23–26 weeks; n=41), (B) very (GA: 27–29 weeks; n=39), and (C) moderately preterm infants (GA: 30–32 weeks; n=33). Blood samples were drawn from the study participants on the 5th and 28th day of life (DOL). The mRNA samples were evaluated for gene expression with the use of GeneChip Human Gene 1.0ST microarrays. Differential expression analysis revealed small subsets of genes that presented positive or negative monotone trends in both the 5th (138 genes) and 28th DOL (308 genes) in the three subgroups of patients. Based on pathway enrichment analysis, we found that most of the pathways that revealed a positive monotone trend were involved in host immunity. The most significantly GA dependent pathways were T-cell receptor signaling pathway and intestinal immune network for IgA production. Overall 4431 genes were differentially expressed between the 5th and 28th DOL. Despite differences in gestational age, patients with the same postconceptional age have a very similar expression of genes