We start with Pseudoxanthoma Elasticum
We are on a mission to find a treatment for all ectopic mineralization disorders. In this long journey, we will start with developing a suitable treatment for Pseudoxanthoma Elasticum, or PXE.
What are ectopic mineralization disorders?
Pseudoxanthoma elasticum (PXE) is a representative example of heritable ectopic mineralization disorders. This condition is characterized by the accumulation of calcium hydroxyapatite crystals in the skin, eyes, and arterial blood vessels. PXE is an autosomal recessive disorder caused by mutations in the ABCC6 gene. Typically, the diagnosis of PXE is made during the second decade of life.
In addition to PXE, there are other disorders within the spectrum of heritable ectopic mineralization. Generalized arterial calcification of infancy (GACI) is one such disorder, characterized by severe arterial calcification that can be identified through prenatal ultrasound or shortly after birth. Another disorder is arterial calcification due to CD73 deficiency (ACDC), which primarily affects older individuals and is characterized by arterial and juxta-articular mineralization. These conditions are caused by mutations in the ENPP1 and NT5E genes, respectively.
The common underlying feature in these three conditions is a decrease in plasma levels of inorganic pyrophosphate (PPi), which is a potent natural inhibitor of ectopic mineralization
The normal function of ABCC6, ENPP1 and CD73 genes found mainly in the liver cells and other tissues are relevant players of plasma PPi balance and factors modifying PPi levels in PXE, GACI and ACDC. Moving the arrow to the left shows how gene mutations affect PPi production, which leads to calcification.
Signs and symptoms of PXE
PXE causes yellowish, thickened patches in flexible skin areas. Blood vessels and eyes can undergo calcification, leading to pain while walking, vision loss, and increased risk of strokes. Stomach blood vessel hardening raises the risk of bleeding.