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Keywords:

  • congenital hypophosphatasia;
  • enzyme replacement-therapy;
  • alkaline phosphatase;
  • bone morphology

ABSTRACT

Weninger, M., Stinson, R. A., Plenk, H. Jr, Böck, P. and Pollak, A. (Division of Neonatology, Department of Paediatrics, the Bone and Biomaterials Research Laboratory, Institution of Histology and Embryology and Institute of Micromorphology and Electron Microscopy, University of Vienna, Vienna, Austria and Division of Clinical Pathology, Department of Pathology, University of Alberta, Edmonton, Canada). Acta Paediatr Scand Suppl 360: 154, 1989.

Enzyme replacement-therapy for a severely affected premature boy (birthweight: 2 380 g, GA: 36 weeks) with hypophosphatasia was attempted by infusions of purified human hepatic alkaline phosphatase. Treatment (1.2 IU/kg/min) started at age three weeks and was repeated in weekly intervals until age 10 weeks, when the child died. Samples of alkaline phosphatase were diluted with 10 ml of physiological saline and infused over 30 min via an umbilical arterial catheter. No toxic or allergic side effects were observed. Serum alkaline phosphatase activity increased from 3 IU/L before treatment to a maximum level of 195 IU/L with a half-life time between 37 and 62 hours. Urinary excretion of phosphoethanolamine decreased during therapy from a maximal level of 9.5 to 5.5 μmol/mg creatinine (normal: <0.4 μmol/mg creatinine). Calcium, phosphorus, parathormone and 1,25-diOH vitamin D levels were within normal range. Sequential radiographic studies showed no improvement of bone mineralization. Bone morphology was studied by light and electron microscopy before treatment and post mortem. The borderline between mineralized and unmineralized matrix was more distinct after treatment and on the electron microscopical level initial spots of mineralization were more frequent between the collagen fibrils compared to the biopsy specimen before treatment. In contrast to previous studies however, only woven and bundle bone structures were studied from the tibial crest, where the lack of osteoblast-like cells upon the newly formed osteoid matrix was prominent.