1. Introduction
OMIM 264800, calcification of the skin, calcification, PXE
RARE DISEASE, DISEASES, PSEUDOXANTHOMA ELASTICUM
Both authors contributed as senior authors.Pseudoxanthoma elasticum (PXE) is characterized by low levels of inorganic pyrophosphate (PPi) and a high activity of tissue-nonspecific alkaline phosphatase (TNAP). Lansoprazole is a partial inhibitor of TNAP. The aim was to investigate whether lansoprazole increases plasma PPi levels in subjects with PXE. We conducted a 2 × 2 randomized, double-blind, placebo-controlled crossover trial in patients with PXE. Patients were allocated 30 mg/day of lansoprazole or a placebo in two sequences of 8 weeks. The primary outcome was the differences in plasma PPi levels between the placebo and lansoprazole phases. 29 patients were included in the study. There were eight drop-outs due to the pandemic lockdown after the first visit and one due to gastric intolerance, so twenty patients completed the trial. A generalized linear mixed model was used to evaluate the effect of lansoprazole. Overall, lansoprazole increased plasma PPi levels from 0.34 ± 0.10 µM to 0.41 ± 0.16 µM (Pseudoxanthoma elasticum (PXE, OMIM 264800, ORPHA 758) is a rare disease caused by biallelic variants of the ABCC6 gene, which encodes an ABC transporter primarily found in the hepatic and renal tissues [In addition to the ABC proteins, PPi levels are regulated by two enzymes: tissue-nonspecific alkaline phosphatase (TNAP), which transforms PPi into two molecules of Pi, and the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) that produces PPi from ATP. We and others have shown that TNAP activity is increased and PPi is reduced in PXE subjects compared with controls [There is no specific treatment to stop progressive calcification in PXE. PPi supplementation has been tested in animal models through its addition to drinking water [There have been few clinical trials in PXE. One trial in PXE patients with oral magnesium supplementation for 2 years was not able to show benefit in terms of reducing calcification of the skin and there were no changes in retinal signs [Lansoprazole is a proton-pump inhibitor licensed to treat diseases related to gastric acid output. Lansoprazole has been shown to partially inhibit the effects of TNAP [