Genetics in Arterial Calcification: Lessons Learned From Rare Diseases

Arterial calcification significantly contributes to morbidity and mortality. Insight into the pathophysiological mechanisms contributing to arterial calcification has come from genetic studies on four rare monogenic disorders. The disease-causing molecular defects in generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE), calcification of joints and arteries (CALJA), and familial idiopathic basal ganglia calcification (IBGC) have been identified within recent years. Based on the similarities of GACI, PXE, CALJA, and IBGC, it can be speculated that the underlying disease genes—ENPP1, ABCC6, NT5E, and SLC20A2, respectively—drive a cohesive molecular pathophysiology system modulated by ATP metabolism, inorganic pyrophosphate, adenosine, and inorganic phosphate generation and functional activities.