Although it has been hypothesized that early biosynthesis defects result in more degradation than secretion of AP, compared with later biosynthesis defects [60,61], the identification of pathogenic variants of PIGW and PIGY in HPMRS5 and HPMRS6, respectively, may suggest other mechanisms of hyperphosphatasia. This evidence concerns the gene DHCR7-DT and Elevated circulating alkaline phosphatase concentration.