Figure 1. (A) Pathophysiology of bone demineralization in hypophosphatasia. (B) Pathophysiology of seizure in hypophosphatasia. A. Mineralization begins with the formation of hydroxyapatite crystals from calcium and phosphate (Pi). Inorganic pyrophosphate (PPi) inhibits the formation of hydroxyapatite crystals. Thus, it must be hydrolyzed by alkaline phosphatase (TNSALP) for mineralization to occur. With the reduced TNSALP activity in hypophosphatasia, PPi is not hydrolyzed, and bone mineralization is decreased. B. In the most severe cases of hypophosphatasia, pyridoxal 5'-phosphate (PLP) is not dephosphorylated effectively, and pyridoxal (PL) becomes unable to cross the blood-brain barrier and participate in the formation of gamma-aminobutyric acid (GABA). This leads to vitamin B6-dependent seizure.