Pyrophosphate (PPi) measurement
Pyrophosphate (PPi) measurement service in our lab is available from Sep 2021!
Although serum PPi level has been recognized to be related to the development of following disorders, there hasn’t been robust assay system for many reasons and only a few limited institutions conducted the assay of PPi. Thus, there have been scarce data regarding PPi levels in the clinical and research setting.
Local excessive PPi in the bone is known to prohibit calcification and high serum PPi level is associated to the development of calcium pyrophosphate deposition disease (CPPD disease) including typical pseudogout due to accumulated calcium pyrophosphate crystal in the joint spaces. Contrarily, low serum PPi has been revealed to associated with the development of calcification of the arterial medium.
Three molecules (ALP, ABCC6, ENPP1) are identified to play a pivotal role for modulating serum and regional PPi levels. ALP (aka TNSALP, ALPL): a membranous protein catabolizes PPi to inorganic phosphates (PPi⇒Pi+Pi), therefore, hypophosphatasia due to loss of function of ALPL causes impaired calcification of the bone resulted in the development of rickets/osteomalacia, as well as increased risk of the induction of CPPD disease.
On the other hand, ABCC6: a membranous protein transports ATP from cytoplasm to outside the cell and ENPP1: also, a membranous protein catabolizes ATP to AMP and PPi (ATP⇒AMP+PPi). As such, homozygous loss-of-function mutations of ABCC6 or ENPP1 causes decreased serum PPi levels and subsequent generalized arterial calcification of infancy (GACI) with significant calcification of arterial media and high mortality of 50 % until 6 months old. Among the survivors of GACI or who avoided GACI, the patients with homozygous loss-of-function mutations of ENPP1 could develop autosomal recessive hypophosphatemic rickets/osteomalacia: a type of FGF23-related hypophosphatemic rickets/osteomalacia with significant ectopic ossifications including ossifications of posterior longitudinal ligament (OPLL), whereas homozygous loss-of-function mutations of ABCC6 could lead to the development of pseudoxanthoma elastica (PXE) with characteristic disseminated subcutaneous calcifications.
Our lab is now open for the requests of PPi measurement for the clinical cases with possible PPi derangement, samples of clinical researches or basic researches.
Please, note that plasma samples for PPi measurements should be subject to centrifugation with particular filter for the protein removal within one hour after blood drawing. Therefore, please, contact us before the collection of samples.
Please, contact us to request PPi measurements by filling the contact form attached below and we’ll reply in one week.