ESPE Abstracts

Background: Hypophosphataemic rickets is a rare, and challenging condition to diagnose as the biochemical and radiological features are subtle compared with the more common calcipaenic rickets. Retrospective review of 4yr-old girl with PHEX mutation initially managed as Blount’s disease with surgery showed low (0.93 mmol/l), but within reference interval phosphate levels at initial presentation which caused some diagnostic uncertainty. Paediatric phosphate reference intervals in use at the time were from UK Pathology Harmony Group (PHG). The aim of the study was to generate indirect reference intervals using local phosphate data and compare these to both PHG and published direct reference intervals in order to determine more appropriate reference intervals and potentially improve the diagnosis of hypophosphatemic rickets.

Methods: Using open source software we applied two different indirect statistical methods – Hoffman (H) and Bhattacharya (B) to generate reference intervals on anonymised data collected during the clinical care of patients. A total of 7094 inpatient, outpatient and community phosphate results were used, all of which had been generated between Jan 2020 and April 2021 using Siemens ADVIA 2400 analysers. We used the same age groupings as published paediatric phosphate reference interval data from the Canadian Laboratory Initiative on Paediatric Reference Limits (CALIPER) group, which had been generated in equivalent laboratory instrumentation.

Results: The two different indirect methods generated very similar reference intervals at each age group. Direct comparison of these locally generated reference intervals with PHG and CALIPER showed that of the 6 reference age groups (<1 month, 1 month-1yr, 1-5yr, 5-13yr, 13-16yr and 16-18 yr), PHG, CALIPER and locally generated reference intervals were very similar apart from 1-5yr and 5-13 yr. In these age groups, the lower limit from the PHG was significantly lower than the published CALIPER lower limit; 0.9 vs 1.42 mmol/l for 1-5yrs and 0.9 vs 1.29 mmol/l for 5-13yr. The indirect methods provided lower limits for these age groups that were intermediate between PHG and CALIPER ranges; 1.17 (H) and 1.21 (B) mmol/l for age 1-5yr and 1.08 (H) and 1.09 (B) mmol/l for age 5-13yr.

Conclusion: Indirect methods can be used to generate paediatric reference intervals from routinely collected local laboratory data. These reference intervals can be used to verify published direct reference intervals or to generate more appropriate intervals for the local population.

Keywords: Hypophosphataemic rickets, phosphate