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 PIGW and Elevated circulating alkaline phosphatase concentration.