TY - JOUR
T1 - Infantile hypophosphatasia
T2 - Normalization of circulating bone alkaline phosphatase activity followed by skeletal remineralization. Evidence for an intact structural gene for tissue nonspecific alkaline phosphatase
AU - Whyte, Michael P.
AU - Magill, H. Lynn
AU - Fallon, Michael D.
AU - Herrod, Henry G.
N1 - Funding Information:
Supported in part by a Grant-in-Aid from the Shriners Hospitals for Crippled Children and by Grant RR-00036 from the General Clinical Research Center Branch, Division of Research Facilities and Resources, National Institutes of Health. Presented in part at the National Meeting, American Federation for Clinical Research, Washington, D.C., May 4 to 7, 1984 (Clin Res 1984;32:290A). Submitted for publication May 15, 1985; accepted July 9, 1985. Reprint requests: Michael P. Whyte, M.D., Jewish Hospital, 216 S. Kingshighway, St. Louis, MO 63110.
PY - 1986/1
Y1 - 1986/1
N2 - After a 3-month course of weekly intravenous infusions of pooled normal plasma in an attempt at enzyme replacement therapy, we observed gradual and prolonged normalization of circulating alkaline phosphatase (AP) activity in a boy with infantile hypophosphatasia. During this 4-month period, when hypophosphatasemia had been corrected, electrophoretic and heat denaturation studies suggested that the AP in serum was skeletal in origin. Serial radiographic and histologic studies of bone demonstrated skeletal remineralization and the appearance of AP activity in osteoblasts and chondrocytes after the infusions. Considerable clinical improvement coincided with the skeletal remineralization. Our observations indicate that in one patient with infantile hypophosphatasia the structural gene for the tissue-nonspecific (bone/liver/kidney) AP isoenzyme was intact and could be expressed with marked physiologic effect. Infantile hypophosphatasia may result from absence or inactivation of a circulating factor(s) that regulates the expression of the gene for tissue nonspecific AP.
AB - After a 3-month course of weekly intravenous infusions of pooled normal plasma in an attempt at enzyme replacement therapy, we observed gradual and prolonged normalization of circulating alkaline phosphatase (AP) activity in a boy with infantile hypophosphatasia. During this 4-month period, when hypophosphatasemia had been corrected, electrophoretic and heat denaturation studies suggested that the AP in serum was skeletal in origin. Serial radiographic and histologic studies of bone demonstrated skeletal remineralization and the appearance of AP activity in osteoblasts and chondrocytes after the infusions. Considerable clinical improvement coincided with the skeletal remineralization. Our observations indicate that in one patient with infantile hypophosphatasia the structural gene for the tissue-nonspecific (bone/liver/kidney) AP isoenzyme was intact and could be expressed with marked physiologic effect. Infantile hypophosphatasia may result from absence or inactivation of a circulating factor(s) that regulates the expression of the gene for tissue nonspecific AP.
UR - http://www.scopus.com/inward/record.url?scp=0022637532&partnerID=8YFLogxK
U2 - 10.1016/S0022-3476(86)80773-9
DO - 10.1016/S0022-3476(86)80773-9
M3 - Article
C2 - 3944698
AN - SCOPUS:0022637532
SN - 0022-3476
VL - 108
SP - 82
EP - 88
JO - The Journal of Pediatrics
JF - The Journal of Pediatrics
IS - 1
ER -