TY - JOUR
T1 - Infantile hypophosphatasia
T2 - Enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease
AU - Whyte, Michael P.
AU - Valdes, Roland
AU - Ryan, Lawrence M.
AU - McAlister, William H.
N1 - Funding Information:
From the Division of Bone and Mineral Metabolism, Department of Medicine, Washington University School of Medicine; Department of Pathology and Laboratory Medicine, The Jewish Hospital of St. Louis, Washington University School of Medicine, Division of Rheumatology, Department of Medicine, The Medical College of Wisconsin; and Section of Pediatric Radiology, Mallinekrodt Institute of Radiology, Washington University School of Medicine. Supported by a research grant (RR-O0036) from the General Clinical Research Center Branch, Division of Research Facilities and Resources, National Institutes of Health; a grant-in-aid from the Shriners Hospitals for Crippled Children (St. Louis Unit); and National Institutes of Health Grant AM-18047.
PY - 1982/9
Y1 - 1982/9
N2 - 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 tissues rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.
AB - 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 tissues rather than blood. Study of additional cases of hypophosphatasia will be necessary to assess the clinical efficacy of this form of enzyme replacement therapy.
UR - http://www.scopus.com/inward/record.url?scp=0019965925&partnerID=8YFLogxK
U2 - 10.1016/S0022-3476(82)80061-9
DO - 10.1016/S0022-3476(82)80061-9
M3 - Article
C2 - 7108657
AN - SCOPUS:0019965925
SN - 0022-3476
VL - 101
SP - 379
EP - 386
JO - The Journal of Pediatrics
JF - The Journal of Pediatrics
IS - 3
ER -