Heritable Ectopic Mineralization Disorders: Pathomechanisms and Potential Treatment

Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic mineralization disorders, is an autosomal recessive disease characterized by deposition of calcium hydroxyapatite in the skin, eyes, and cardiovascular system, with protean manifestations (Li et al., 2016; Li and Uitto, 2013; Neldner, 1988). The classic form of PXE is late-onset and slow-progressing, and the major clinical problems relate to loss of vision and development of cardiovascular complications (Neldner, 1988). The classic form of PXE is caused by loss-of-function mutations in the ABCC6 gene encoding ATP-binding cassette subfamily C, member 6 (ABCC6), a putative transmembrane efflux transporter protein expressed primarily in the liver and kidneys. The metabolic hypothesis concerning PXE postulates that the absence of functional ABCC6 activity, primarily in the liver, results in deficiency of circulating factor(s) that is physiologically required to prevent ectopic mineralization under normal calcium and phosphate homeostasis (Li et al., 2016) (Figure 1). However, the factor(s) transported by ABCC6 from the intracellular milieu to the extracellular space have not been identified.