Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. J Pediatr 1982 Sep;101(3):379-86
Date
09/01/1982Pubmed ID
7108657DOI
10.1016/s0022-3476(82)80061-9Scopus ID
2-s2.0-0019965925 (requires institutional sign-in at Scopus site) 77 CitationsAbstract
Enzyme replacement therapy for a severely affected 6-month-old girl with hypophosphatasia was attempted by repeated intravenous infusions of alkaline phosphatase-rich plasma, obtained by plasmapheresis, from two men with Paget bone disease. Circulating Paget AP activity was found to have a half-life (two days) similar to that reported in adults, which did not change during a five-week period of six AP infusions. Normalization of the patient's serum AP activity was followed by better control of her hypercalcemia and hypercalciuria. Sequential radiographic studies revealed arrest of worsening rickets with slight remineralization of metaphyses, although urinary excretion of the AP substrates phosphoethanolamine and inorganic pyrophosphate was unaltered by therapy. Our findings suggest that the infantile form of hypophosphatasia results from defective production of AP rather than from accelerated destruction of circulating enzyme, and that hydrolysis of AP substrates like PEA and PPi occurs primarily in tissue rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.
Author List
Whyte MP, Valdes R Jr, Ryan LM, McAlister WHMESH terms used to index this publication - Major topics in bold
Alkaline PhosphataseFemale
Humans
Hypophosphatasia
Infant
Infusions, Parenteral
Male
Osteitis Deformans
Plasma
Plasmapheresis