<unk>  is associated with a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including mineralization-inhibiting inorganic pyrophosphate (PPi) and pyridoxal 5’-phosphate (PLP), a major form of vitamin B. A relationship describing physiologic regulation of mineralization has been termed the Stenciling Principle of mineralization, whereby enzyme-substrate pairs imprint mineralization patterns locally into the extracellular matrix (most notably described for bone) by degrading mineralization inhibitors (e.g. TNAP/TNSALP/ALPL enzyme degrading the pyrophosphate inhibition of mineralization, and PHEX enzyme degrading the osteopontin inhibition of mineralization). The Stenciling Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in<unk>  <unk>  and X-linked hypophosphatemia (XLH).6. When TSNALP enzymatic activity is low, inorganic pyrophosphate (PPi) accumulates outside of cells in the extracellular matrix of bones and teeth, and inhibits formation of hydroxyapatite mineral, the main hardening component of bone, causing rickets in infants and children and osteomalacia (soft bones) and odontomalacia (soft teeth) in children and adults. PLP is the principal form of vitamin B6 and must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters, which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate (CPPD) crystals in the joint can cause pseudogout.
Hypophosphatasia
Hypoprolactinemia
Hypervalinemia
Osteomalacia
Hyperphosphatasia with mental retardation syndrome
Hyperprolinemia
Methaemalbuminaemia
Hypophosphatemia