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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Alkaline phosphatase deficiency in cultured skin fibroblasts from patients with hypophosphatasia: comparison of the infantile, childhood, and adult forms.

Alkaline phosphatase (AP) activity was assayed by a sensitive fluorometric method, using 4-methylumbelliferyl phosphate as substrate, in homogenates of confluent skin fibroblasts from 17 patients with the infantile, childhood, or adult form of hypophosphatasia and compared to the AP activity in 22 sex- and age-matched control cell lines. Statistically significant deficiency of AP activity was found in all 3 types of hypophosphatasia (8.2%, 30.2% and 18.5% of control values, respectively); however, there was considerable variation of enzyme activity, especially in the control groups, and some overlap between patient and control values occurred for the childhood and adult age groups. These fibroblast studies suggest that all clinical forms of hypophosphatasia are characterized by deficient activity of the bone/liver/kidney AP isoenzyme. The clinical severity of the infantile form is reflected by a profound lack of AP activity in cultured skin fibroblasts. Further study will be necessary to determine the mechanism(s) of the deficiency in AP activity in each form of hypophosphatasia. Nevertheless, we suggest that AP-deficient infantile hypophosphatasia skin fibroblasts in culture might constitute a good tool by which to explore the unknown physiological role of AP.[1]


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