Inborn error of metabolism characterized by low serum alkaline phosphatase activity from loss of function mutations.

Loss of function mutations are typically missense within the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP).

Substrates of TNSALP accumulate, including inorganic pyrophosphate, an inhibitor of minerlization, and pyridoxal 5’phosphate (PLP) the major circulating form of circulating vitamin B6.

High levels of extracellular inorganic pyrophosphate blocks hydroxyapatite crystal growth and results in rickets or osteomalacia.

Affected patients may have hypercalcemia, and hyperphosphatemia.

Associated with impaired vitamin B6 metbolism indicating that TNSALP functions as a cell surface enzyme.

When TNSALP deficiency is profound pyrioxine responsive seizures may occur.

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