title: Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene.
abstract: We report the case of a male patient with infantile hypophosphatasia associated with severe hypercalcaemia and mild respiratory insufficiency. At the age of 2 months, severe hypercalcaemia, low levels of serum alkaline phosphatase activity, and elevated urinary excretion of calcium and phosphoethanolamine were noted. Radiological findings showed generalized osteopenia and disturbed and irregular ossification of the metaphyses. Their involvement had spontaneously improved at the age of 6 months. A genetic study revealed that the tissue-nonspecific alkaline phosphatase gene of the patient had two novel mutations, K207E and G409C, derived from the mother and father, respectively. A reconsitution experiment revealed that both mutant gene products had low but significant enzymatic activity.
  
  
  CONCLUSIONS
  The detection of tissue-nonspecific alkaline phosphatase gene mutations and expression studies to determine the enzymatic activity of mutant gene products was useful for assessing the clinical course of this patient with hypophosphatasia.
authors.affiliation: Division of Endocrinology and Metabolism, Saitama Children's Medical Centre, Japan. h-mochi@zb3.so-net.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Mochizuki
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Michigami
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: N
authors.initials: N
authors.lastname: Koda
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology*; D007014:Hypophosphatasia / Q000150:complications / Q000235:genetics*; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012131:Respiratory Insufficiency / Q000209:etiology*; D017422:Sequence Analysis, DNA
chemical_list: D000469:Alkaline Phosphatase