TY - JOUR
T1 - Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate
T2 - Clinical and laboratory aspects
AU - Caswell, Alison M.
AU - Whyte, Michael P.
AU - Russell, R. Graham G.
N1 - Funding Information:
A. M. Caswell was supported by grants from the Royal Society, U.K., and from Action Research for the Crippled Child, U.K. M. P. Whyte was supported by Grants 15958 and 15963 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. We are grateful to Dr. Michael D. Fallon, Department of Surgical Pathology, Thomas Jefferson University School of Medicine, Philadelphia, for providing the histopathological sections for reproduction.
PY - 1991
Y1 - 1991
N2 - Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. The clinical expression of the disease is highly variable, but in early life the severity tends to reflect the age of onset. Accordingly, the disease is often classified into perinatal, infantile, and childhood forms. Hypophosphatasia also occurs in adults. Some exhibit symptoms in adulthood for the first time, but others have a history of the disease in early life with an intervening symptom-free period. Defective mineralization of bones and teeth is the predominant clinical feature of all forms of the disease. Biochemically, the reduction in ALP activity is associated with alterations in the extracellular metabolism of various phosphorylated compounds, including inorganic pyrophosphate (PPi), phosphoethanolamine, and pyridoxal 5's-phosphate. Of these, PPi may have an especially important role in the development of the mineralization defect. Accordingly, the extracellular metabolism of PPi and its possible role in the regulation of mineralization will be discussed.
AB - Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. The clinical expression of the disease is highly variable, but in early life the severity tends to reflect the age of onset. Accordingly, the disease is often classified into perinatal, infantile, and childhood forms. Hypophosphatasia also occurs in adults. Some exhibit symptoms in adulthood for the first time, but others have a history of the disease in early life with an intervening symptom-free period. Defective mineralization of bones and teeth is the predominant clinical feature of all forms of the disease. Biochemically, the reduction in ALP activity is associated with alterations in the extracellular metabolism of various phosphorylated compounds, including inorganic pyrophosphate (PPi), phosphoethanolamine, and pyridoxal 5's-phosphate. Of these, PPi may have an especially important role in the development of the mineralization defect. Accordingly, the extracellular metabolism of PPi and its possible role in the regulation of mineralization will be discussed.
KW - Alkaline phosphatase
KW - Hypophoshatasia
KW - Inorganic pyrophosphate
KW - Mineralization
UR - http://www.scopus.com/inward/record.url?scp=0025856050&partnerID=8YFLogxK
U2 - 10.3109/10408369109106863
DO - 10.3109/10408369109106863
M3 - Article
C2 - 1647780
AN - SCOPUS:0025856050
VL - 28
SP - 195
EP - 232
JO - Critical Reviews in Clinical Laboratory Sciences
JF - Critical Reviews in Clinical Laboratory Sciences
SN - 1040-8363
IS - 3
ER -