Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene

We report the case of a male patient with infantile hypophosphatasia associ ated with severe hypercalcaemia and mild respiratory insufficiency. At the age of 2 months, severe hypercalcaemia, low levels of serum alkaline phosph atase activity, and elevated urinary excretion of calcium and phosphoethano lamine were noted. Radiological findings showed generalized osteopenia and disturbed and irregular ossification of the metaphyses. Their involvement h ad spontaneously improved at the age of 6 months. A genetic study revealed that the tissue-nonspecific alkaline phosphatase gene of the patient had tw o novel mutations, K207E and G409C, derived from the mother and father, res pectively. A reconsitution experiment revealed that both mutant gene produc ts had low but significant enzymatic activity. Conclusion The detection of tissue-nonspecific alkaline phosphatase gene mu tations and expression studies to determine the enzymatic activity of mutan t gene products was useful for assessing the clinical course of this patien t with hypophosphatasia.