An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of...

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease affecting tissues rich in elastic fibers such as the skin, retina, and cardiovascular system. Mutations in the ABCC6 gene are known to be causative in most patients. Generalized arterial calcification of infancy (GACI) is characterized by extensive hydroxyapatite deposits in the internal elastic laminae in large and medium-sized arteries, leading to arterial stenoses and early and severe myocardial ischemia. GACI has been found to be primarily caused by mutations in the ENPP1 gene. We report two brothers born to unrelated parents. The elder developed uncomplicated PXE in adolescence and harbored mutations in the ABCC6 gene. The younger child died of a condition strikingly reminiscent of GACI at 15 months of age. This case of GACI was independent of mutations in the ENPP1 gene but was probably related to ABCC6 mutations. We demonstrate that matrix Gla protein and fetuin-A, involved in PXE, are also expressed in this case of GACI. These proteins could act as local and systemic inhibitors to limit the extension of mineralization. This report emphasizes concurrently that ABCC6 may be a relevant candidate gene in some cases of GACI with no mutations in the ENPP1 gene, and that GACI may be an atypical and severe end of the vascular phenotype spectrum of PXE.