Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres.

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An average of 1.7 RFE per consultation and a broad clinical spectrum of problems were presented in primary care; nevertheless, 94.3% of all problems were solved in primary care, reflecting the crucial role of PCPs as a coordinator of healthcare.

In preterm neonates, in-hospital mortality does not significantly differ across racial and ethnic groups. However, in very preterm infants, in-hospital mortality for Black neonates is improved. There are morbidity differences (RDS, ROP) seen among racial/ethnic groups.

Due to the favourable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, e.g. birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

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Assimilatory sulfate reduction supplies prototrophic organisms with reduced sulfur that is required for the biosynthesis of all sulfur-containing metabolites, including cysteine and methionine. The reduction of sulfate requires its activation via an ATP-dependent activation to form adenosine-5′-phosphosulfate (APS). Depending on the species, APS can be reduced directly to sulfite by APS reductase (APR) or undergo a second phosphorylation to yield 3′-phosphoadenosine-5′-phosphosulfate (PAPS), the substrate for PAPS reductase (PAPR). These essential enzymes have no human homolog, rendering them attractive targets for the development of novel antibacterial drugs. APR and PAPR share sequence and structure homology as well as a common catalytic mechanism, but the enzymes are distinguished by two features, namely, the amino acid sequence of the phosphate-binding loop (P-loop) and an iron-sulfur cofactor in APRs. Based on the crystal structures of APR and PAPR, two P-loop residues are proposed to determine substrate specificity; however, this hypothesis has not been tested. In contrast to this prevailing view, we report here that the P-loop motif has a modest effect on substrate discrimination. Instead, by means of metalloprotein engineering, spectroscopic and kinetic analyses, we demonstrate that the iron-sulfur cluster cofactor enhances APS reduction by nearly 1000-fold, thereby playing a pivotal role in substrate specificity and catalysis. These findings offer new insights into the evolution of this enzyme family, and extend the known functions of protein-bound iron-sulfur clusters.

Objective: To compare the incidence of chronic lung disease (CLD) in extremely low birth weight (ELBW, p1000 g) infants before and after the introduction of early, preferential application of nasal continuous airway pressure (NCPAP) utilizing a variable flow delivery system. Study design:A retrospective cohort study of ELBW infants 2 years prior to (Pre-early NCPAP, n ¼ 96) and 2 years following (Early NCPAP, n ¼ 75) the initiation of an early NCPAP policy.Results: There were no significant changes (Pre-early NCPAP vs Early NCPAP) in the incidences of CLD (35 vs 33%, P ¼ 0.81) or CLD or death (50 vs 43%, P ¼ 0.34). Infants in the Early NCPAP group weaned off mechanical ventilation and supplemental oxygen more rapidly than infants in the Pre-early NCPAP group (hazard ratio (HR) 1.80, P ¼ 0.002 and HR 1.69, P ¼ 0.01). Conclusion:A policy of early NCPAP has not decreased the incidence of CLD despite a decrease in time to successful tracheal extubation.