The concept of ENPP1-deficiency has evolved dramatically over the past several decades: what once considered an exclusively fatal arterial disease with poor prognosis is now recognized as a complex, multi-systemic process with a broad phenotypic spectrum spanning from infantile vascular calcification associated with early demise, to hypophosphatemic rickets in survivors, and as indicated in this study, to typical late-onset PXE with more favorable prognosis and normal life expectancy. This evidence concerns the gene ENPP1 and hypophosphatemic rickets.