Tissue-nonspecific alkaline phosphatase (TNAP) is an enzyme present on the surface of
mineralizing cells and their derived matrix vesicles that promotes hydroxyapatite crystal
growth. Hypophosphatasia (HPP) is an inborn-error-of-metabolism that, dependent upon
age of onset, features rickets or osteomalacia due to loss-of function mutations in the gene
(Alpl) encoding TNAP. Craniosynostosis is prevalent in infants with HPP and other forms of
rachitic disease but how craniosynostosis develops in these disorders is unknown …

53 Hypophosphatasia (HPP) is an inborn-error-of-metabolism that, 54 dependent upon age
of onset, features rickets or osteomalacia due to loss-of function mutations in the gene (Alpl)
encoding the tissuenonspecific alkaline phosphatase isozyme (TNAP or TNSALP)[1–4].
Clinical manifestations of HPP are broad-ranging both in terms of severity and age of onset,
with more severe forms of the disorder 59 presenting in utero or infancy [5]. The HPP
phenotype is primarily char-60 acterized by defective bone mineralization as a result of …