Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach.

In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an "Other disorder suspected" (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020.

Inaccuracies in plasma oxytocin extraction and enzyme immunoassay techniques.

Numerous studies have reported extensive associations between plasma oxytocin (OXT) concentrations and various human physiological and neurobehavioral processes. Measurement of OXT is fraught with difficulty due to its low molecular weight and plasma concentrations, with no consensus as to the optimal conditions for pre-analytical sample extraction, standards for immunoassay validation or the ideal protease inhibitors to prevent OXT degradation. Previous attempts at determining the efficacy of various purification techniques such as solid phase extraction (SPE) or ultrafiltration have only utilized human plasma samples, making it difficult to dissect out whether the effect of interference comes from the extraction process itself or cross-reactivity with other proteins.

Cross-sectional audit assessing the quality of dried bloodspot specimens received by UK metabolic biochemistry laboratories for the biochemical monitoring of individuals with Phenylketonuria.

Background: Sapropterin has been approved as a treatment option for individuals with Phenylketonuria in the United Kingdom. Individuals are assessed as responsive to Sapropterin by a ≥30% reduction in Phenylalanine (Phe) concentrations using dried blood spot (DBS) specimens. DBS quality is critical for accurate and precise measurement of Phe.

UK National audit of the measurement of ammonia.

Background: Severe hyperammonaemia is associated with significant morbidity and mortality. Rapid analysis and reporting of ammonia results is essential to prevent patient harm. The aim was to investigate the laboratory sample acceptance criteria, ammonia analysis and the reporting of ammonia results.

A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD).

Context: Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important.

Objective: We aimed to better understand the presentation and prevalence of pediatric DSD.

Establishing risk factors and outcomes for congenital hypothyroidism with gland in situ using population-based data linkage methods: study protocol.

Introduction: There has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted for by an increase in CH with gland in situ (CH-GIS). It is not known why CH-GIS is becoming more common, nor how it affects the health, development and learning of children over the long term.

Free 25-hydroxyvitamin-D concentrations are lower in children with renal transplant compared with chronic kidney disease.

Background: Total serum 25-hydroxyvitamin D [25(OH)D] is considered the best marker of vitamin D status and used routinely in clinical practice. However, 25(OH)D is predominantly bound to vitamin D-binding protein (VDBP), and it has been reported that the free-25(OH)D and 25(OH)D loosely bound to albumin fraction correlates better with clinical outcomes.

Methods: We assessed total-25(OH)D, measured free-25(OH)D, and calculated free-25(OH)D and their relationship with VDBP and biomarkers of mineral metabolism in 61 children (22 CKD 2-3, 18 dialysis, and 21 post-transplant).

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

Background: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce.

Methods: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children.

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children.

Unlabelled: Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8-15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis time constant.

Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease.

Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD).

Measuring Erythrocyte Thiopurine Methyltransferase Activity in Children-Is It Helpful?

Objective: To assess the profile of thiopurine transmethyltransferase (TPMT) enzyme activities in children and discuss the utility of measuring TPMT levels before commencing azathioprine therapy.

Study Design: Retrospective study in a single pediatric center of all patients who had TPMT enzyme assay measured during a 3-year period before the start of azathioprine therapy. Patients' TPMT enzyme activities were classified as normal (26-50 pmol/h/mgHb), intermediate (10-25 pmol/h/mgHb), and deficient (<10 pmol/h/mgHb).

Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD.

Angiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort.

Establishment of paediatric age-related reference intervals for serum prolactin to aid in the diagnosis of neurometabolic conditions affecting dopamine metabolism.

Background: There are a number of inborn errors of dopamine biosynthesis for which prolactin measurement may be a useful screening tool. However, the interpretation of prolactin results is difficult as age-related paediatric reference intervals are scant especially in infancy.

Methods: Serum prolactin reference intervals were calculated from the existing laboratory data using an indirect method, based on patients (n = 2369) attending a tertiary care hospital over a 10-year period.

Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial.

Background And Objectives: Vitamin D deficiency is an important contributor to the development of hyperparathyroidism and is independently associated with cardiovascular and bone disease. The hypothesis was that nutritional vitamin D (ergocalciferol) supplementation in children with CKD stages 2-4 delays the onset of secondary hyperparathyroidism.

Design, Setting, Participants, & Measurements: A randomized, double-blinded, placebo-controlled study in children with CKD2-4 who had 25-hydroxyvitamin D [25(OH)D] deficiency was conducted.