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Objectives Increasingly, laboratories flag low serum alkaline phosphatase (sALP) that are age-and sex-specific in paediatrics. The aim of this study was to report clinical manifestations of paediatric patients with age-and sex-specific low sALP, thereby increasing awareness of its potential aetiologies. Methods This retrospective Canadian tertiary care paediatric hospital study assessed all sALP of ambulatory patients aged less than 18 years from 2015 to 2017. The hospital used a Beckman Coulter AU assay to measure sALP and compared values to the Canadian age-and sex-specific reference intervals from CALIPER. All children who had at least one subnormal age-and sex-specific sALP were evaluated. A review of medical charts of included patients was performed and demographic characteristics, medical history and diagnosis were collected, and categorized under groups of medical disorders. Results Of 11,874 included patients, 1,001 patients (9.2%) had low sALP. Of those, 48% (485/1,001) had transient low sALP activity and 9.6% (96/1,001) had persistently low sALP. Prolonged immobilization and inflammatory bowel disease represented the main aetiologies for persistently low sALP. Interestingly, 13.5% (13/96) of patients with persistently low sALP had no apparent aetiology. Conclusions Our results report aetiologies of low sALP in a Canadian paediatric population using age-and sex-specific Canadian reference ranges. This study highlights that healthcare providers should be aware that a low sALP may have clinical significance and should be repeated if warranted based on further clinical assessment. [ABSTRACT FROM AUTHOR]

Recombinant lysine:N6-hydroxylase, rIucD, which is isolated as an apoenzyme, requires FAD and NADPH for its catalytic function. rIucD preparations have been found to undergo time-dependent loss in monooxygenase function due to aggregation from the initial tetrameric state to a polytetrameric form(s), a process which is reversible by treatment with thiols. Ligand-in-duced conformational changes in rIucD were assessed by monitoring its CD spectra, DSC profile, and susceptibility to both endo- as well as exopeptidases. The first two methods indicated the absence of any significant conformational change in rIucD, while the last approach revealed that FAD, and its analog ADP, can protect the protein from the deleterious action of proteases. NADPH was partially effective and L-lysine was ineffective in this regard. Deletion of the C-terminal segment, either by treatment with carboxypeptidase Y or by mutagenesis of iucD, results in the loss of rIucD's monooxygenase activity. These findings demonstrate the crucial role of the C-terminal segment in maintaining rIucD in its native conformation. [ABSTRACT FROM AUTHOR]