Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development.

Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders: Pathomechanisms and Treatment Development. Am J Pathol. 2018 Nov 07;: Authors: Li Q, van de Wetering K, Uitto J Abstract Ectopic mineralization is a global problem and leading cause of morbidity and mortality. The pathomechanisms of ectopic mineralization are poorly understood. Recent studies on heritable ectopic mineralization disorders with defined gene defects have been helpful in elucidation of the mechanisms of ectopic mineralization in general. The prototype of such disorders is pseudoxanthoma elasticum (PXE), a late-onset, slowly progressing disorder with multi-system clinical manifestations. Other conditions include generalized arterial calcification of infancy (GACI) characterized by severe, early-onset mineralization of the cardiovascular system often with early postnatal demise. In addition, arterial calcification due to CD73 deficiency (ACDC) occurs late in life mostly affecting arteries in the lower extremities in elderly individuals. These three conditions, PXE, GACI, and ACDC, caused by mutations in ABCC6, ENPP1, and NT5E, are characterized by reduced levels of inorganic pyrophosphate (PPi) in plasma. Since PPi is a powerful anti-mineralization factor, it has been postulated that reduced PPi is a major determinant for ectopic mineralization in PXE, GACI, and ACDC. These and related observations on complementary mechanisms of ectopic m...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research