ALPL and hypophosphatasia: Hypophosphatasia (HPP) is the rare, inherited, systemic, metabolic disease characterized by low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which leads to extracellular accumulation of its substrates, mainly inorganic pyrophosphate (PPi) and pyridoxal 5′-phosphate (PLP) (1–4).