ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2022 Jan 1;107(1):109-118.Abstract: https://pubmed-ncbi-nlm-nih-gov/34498693/

In Brief: This study established a standard range of Inorganic Pyrophosphate (PPi) between 2.36 and 4.44 µM (5th-95th percentiles) in the blood plasma of children and adolescents aged 0 to 18 years, using the ATP sulfurylase assay. There was no sex difference and the range is similar to previously reported adult ranges of 2-5 µM/L.

Commentary: PPi is a potent inhibitor of mineralisation. Circulating PPi prevents mineralisation to occur in non-osseous tissues while a higher concentration of Alkaline phosphatase (ALP) in bones breaks down PPi to facilitate mineralisation. PPi is generated from ATP in the presence of the ENPP1 enzyme. ATP Sulfurylase converts PPi to ATP; the assay utilises ATP sulfurylase to convert PPi to ATP, which is then detected by a luciferase/luciferin luminescence detection kit.

The analytical sensitivity of the ATP sulfurylase assay ranged from 0.15 to 10 µM PPi. Inter- and intra-assay coefficients of variability on identical samples were good (< 10%). The standard range of PPi in the blood plasma of children and adolescents aged 0 to 18 years was calculated as 2.36 to 4.44 µM, with a median of 3.17 µM, with no sex difference. PPi plasma levels did not differ significantly between different pediatric age groups.

Besides providing normative data on PPi in children, this assay is now validated for use in children. This assay provides an important biomarker for the reliable diagnosis of generalised arterial calcification in infancy (low PPi) and hypophosphatasia (high PPi). Further experience however will be required with the measurement of PPi to identify any other disorders or factors which can contribute to the concentration of PPi. There is also potential to use PPi measurements for titrating the dose of asfotase alfa in hypophosphatasia where overtreatment can lead to extra-skeletal calcifications.