Congenital hypophosphatasia is absence or low levels of serum alkaline phosphatase due to mutations in the gene encoding tissue nonspecific alkaline phosphatase (TNSALP).
Because serum alkaline phosphatase is absent or decreased, calcium is not diffusely deposited in bones, causing low bone density and hypercalcemia. Alkaline phosphatase deficiency also causes intracellular pyridoxine deficiency (vitamin B6 deficiency), which can cause generalized seizures. Vomiting, inability to gain weight, and enlargement of the epiphyses (similar to that in rickets) usually occur. Patients who survive infancy have bony deformities and short stature, but mental development is normal.
Until recently, no treatment was effective, but in 2015, asfotase alfa (a recombinant protein carrying the catalytic domain of tissue nonspecific alkaline phosphatase) subcutaneous injection was approved for treatment of congenital hypophosphatasia. Vitamin B6 in high doses may reduce seizures; 50 to 100 mg IV is given once for an active seizure, followed by 50 to 100 mg po once/day. NSAIDs reduce bone pain. Infusions of alkaline phosphatase and bone marrow transplantation have limited roles.