Parenting a child with phenylketonuria or galactosemia: implications for health-related quality of life

Parents of children with chronic disorders have an impaired health-related quality of life (HRQoL) compared to parents of healthy children. Remarkably, parents of children with a metabolic disorder reported an even lower HRQoL than parents of children with other chronic disorders. Possibly, the uncertainty about the course of the disease and the limited life expectancy in many metabolic disorders are important factors in the low parental HRQoL. Therefore, we performed a cross-sectional study in parents of children with phenylketonuria (PKU, OMIM #261600) and galactosemia (OMIM #230400), metabolic disorders not affecting life expectancy, in order to investigate their HRQoL compared to parents of healthy children and to parents of children with other metabolic disorders. A total of 185 parents of children with PKU and galactosemia aged 1-19 years completed two questionnaires. Parents of children with PKU or galactosemia reported a HRQoL comparable to parents of healthy children and a significantly better HRQoL than parents of children with other metabolic disorders. Important predictors for parental mental HRQoL were the psychosocial factors emotional support and loss of friendship. As parental mental functioning influences the health, development and adjustment of their children, it is important that treating physicians also pay attention to the wellbeing of the parents. The insight that emotional support and loss of friendship influence the HRQoL of the parents enables treating physicians to provide better support for these parents

Outcome of preterm infants with postnatal cytomegalovirus infection

OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life

Rhythmic EEG patterns in extremely preterm infants : Classification and association with brain injury and outcome

Objective: Classify rhythmic EEG patterns in extremely preterm infants and relate these to brain injury and outcome. Methods: Retrospective analysis of 77 infants born &lt;28 weeks gestational age (GA) who had a 2-channel EEG during the first 72 h after birth. Patterns detected by the BrainZ seizure detection algorithm were categorized: ictal discharges, periodic epileptiform discharges (PEDs) and other waveforms. Brain injury was assessed with sequential cranial ultrasound (cUS) and MRI at term-equivalent age. Neurodevelopmental outcome was assessed with the BSITD-III (2 years) and WPPSI-III-NL (5 years). Results: Rhythmic patterns were observed in 62.3% (ictal 1.3%, PEDs 44%, other waveforms 86.3%) with multiple patterns in 36.4%. Ictal discharges were only observed in one and excluded from further analyses. The EEG location of the other waveforms (p &lt; 0.05), but not PEDs (p = 0.238), was significantly associated with head position. No relation was found between the median total duration of each pattern and injury on cUS and MRI or cognition at 2 and 5 years. Conclusions: Clear ictal discharges are rare in extremely preterm infants. PEDs are common but their significance is unclear. Rhythmic waveforms related to head position are likely artefacts.&amp; para;&amp; para;Significance: Rhythmic EEG patterns may have a different significance in extremely preterm infants. (C) 2017 International Federation of Clinical Neurophysiology

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection

OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life

Evaluation of quality of life in PKU before and after introducing tetrahydrobiopterin (BH4), a prospective multi-center cohort study

Phenylketonuria (PKU) is a rare inborn error of metabolism caused by phenylalanine hydroxylase enzyme (PAH) deficiency. Treatment constitutes a strict Phe restricted diet with unpalatable amino acid supplements. Residual PAH activity enhancement with its cofactor tetrahydrobiopterin (BH4) is a novel treatment which increases dietary tolerance in some patients and permits dietary relaxation. Relaxation of diet may improve health related quality of life (HRQoL). This prospective cohort study aims to evaluate HRQoL of patients with PKU and effects of BH4 treatment on HRQoL. Patients aged 4years and older, diagnosed through newborn screening and early and continuously treated, were recruited from eight metabolic centers. Patients and mothers completed validated generic and chronic health-conditions HRQoL questionnaires (PedsQL, TAAQOL, and DISABKIDS) twice: before and after testing BH4 responsivity. Baseline results were compared to the general population. Data collected after BH4 testing was used to find differences in HRQoL between BH4 unresponsive patients and BH4 responsive patients after one year of treatment with BH4. Also a within patient comparison was performed to find differences in HRQoL before and after treatment with BH4. 69/81 (85%) patients completed the questionnaires before BH4 responsivity testing, and 45/69 (65%) participated again after testing. Overall PKU patients demonstrated normal HRQoL. However, some significant differences were found when compared to the general population. A significantly higher (thus better) score on the PedsQL was reported by children 8-12 years on physical functioning and by children 13-17 years on total and psychosocial functioning. Furthermore, adult patients reported significantly lower (thus worse) scores in the TAAQOL cognitive domain. 10 patients proved to be responsive to BH4 treatment; however improvement in their HRQoL after relaxation of diet could not be demonstrate

Targeted Biomarker Discovery by High Throughput Glycosylation Profiling of Human Plasma Alpha1-Antitrypsin and Immunoglobulin A

<div><p>Protein N-glycosylation patterns are known to show vast genetic as well as physiological and pathological variation and represent a large pool of potential biomarkers. Large-scale studies are needed for the identification and validation of biomarkers, and the analytical techniques required have recently been developed. Such methods have up to now mainly been applied to complex mixtures of glycoproteins in biofluids (e.g. plasma). Here, we analyzed N-glycosylation profiles of alpha1-antitrypsin (AAT) and immunoglobulin A (IgA) enriched fractions by 96-well microtitration plate based high-throughput immuno-affinity capturing and N-glycan analysis using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF). Human plasma samples were from the Leiden Longevity Study comprising 2415 participants of different chronological and biological ages. Glycosylation patterns of AAT enriched fractions were found to be associated with chronological (calendar) age and they differed between females and males. Moreover, several glycans in the AAT enriched fraction were associated with physiological parameters marking cardiovascular and metabolic diseases. Pronounced differences were found between males and females in the glycosylation profiles of IgA enriched fractions. Our results demonstrate that large-scale immuno-affinity capturing of proteins from human plasma using a bead-based method combined with high-throughput N-glycan analysis is a powerful tool for the discovery of glycosylation-based biomarker candidates.</p></div

Repeatability of the enrichment procedure with subsequent analysis.

<p>Relative intensities together with their inter-batch standard deviations are depicted for AAT (A) and IgA (B).</p

Peak annotation of IgA-enriched glycans.

<p>Glycan compositions were annotated based on spiking experiments with human plasma and literature. Compositions are given in terms of Hex: hexose, HexNAc: N-acetylhexosamine, Fuc: fucose, NeuAc: N-acetylneuraminic acid.</p