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March 3, 1989, Vol 261, No. 9 >
ARTICLE | March 3, 1989

Benign Familial Hyperphosphatasemia FREE

Patricia A. Siraganian, MD; John J. Mulvihill, MD; Richard A. Mulivor, PhD; Robert W. Miller, MD
[+] Author Affiliations

Reprint requests to Clinical Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 400, Bethesda, MD 20892 (Dr Siraganian).


JAMA. 1989;261(9):1310-1312. doi:10.1001/jama.1989.03420090074034
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References

Elevated alkaline phosphatase activity in serum suggests bone or liver disease or a neoplasm but can also indicate pregnancy or another benign condition. A family with benign hyperphosphatasemia was studied to elucidate the genetics and enzyme defect. Serum total alkaline phosphatase activity was greater than the population mean in all six family members, and more than 7 SDs above the mean in two of four offspring. Monoclonal antibodies to three alkaline phosphatase isoenzymes, intestinal, placental, and tissue nonspecific (liver/bone/kidney), demonstrated markedly increased intestinal alkaline phosphatase levels (29% to 44% of total) in all family members and significantly elevated liver/bone/ kidney activity in the two offspring. Guanidine hydrochloride denaturation of the liver/bone/kidney component showed high alkaline phosphatase activity from liver in both siblings and from bone in one. The mode of inheritance in this family is obscure, but a complex regulation of the products of two different alkaline phosphatase genes seems likely. Steps toward diagnosis are suggested. Early recognition of this benign biochemical abnormality should help to avoid unnecessary diagnostic tests.

(JAMA 1989;261:1310-1312)

REFERENCES

1 +
McComb RB, Bowers GN Jr, Posen S: Alkaline Phosphatase . New York, Plenum Press, 1979;.
2 +
Wilson JW:  Inherited elevation of alkaline phosphatase activity in the absence of disease . N Engl J Med 1979;;301:983-984.
3 +
Parker PH, Ghishan FK:  Asymptomatic familial elevation of serum alkaline phosphatase levels . AJDC 1980;;134:1094-1095.
4 +
McEvoy M, Skrabanek P, Wright E, et al:  Family with raised serum alkaline phosphatase activity in the absence of disease . Br Med J 1981;;282:1272.
5 +
Ducobu J, Dupont P:  Inherited raised alkaline phosphatase activity in the absence of disease . Lancet 1981;;1:1372-1373.
6 +
Nogueras LC, Lleida JV, Badia MS, et al:  Raised serum alkaline phosphatase activity in one family . Arch Intern Med 1982;;142:188-189.
7 +
Kruse K:  Inherited isolated hyperphosphatasemia . Acta Pediatr Scand 1983;;72:833-835.
8 +
Rico H, Martinez F, Romero P, et al:  Benign familial hyperphosphatasemia: A case report . Rev Clin Esp 1987;;180:465-466.
9 +
Mulivor RA, Boccelli D, Harris H:  Quantitative analysis of alkaline phosphatases in serum and amniotic fluid: Comparison of biochemical and immunologic assays . J Lab Clin Med 1985;;105:342-348.
10 +
Shephard MDS, Peake MJ:  Quantitative method for determining serum alkaline phosphatase isoenzyme activity: I. Guanidine hydrochloride: New reagent for selectively inhibiting major serum isoenzymes of alkaline phosphatase . J Clin Pathol 1986;;39:1025-1030.
11 +
Mulivor RA, Hannig VL, Harris H:  Developmental changes in human intestinal alkaline phosphatase . Proc Natl Acad Sci USA 1978;;75:3909-3912.
12 +
McKenna MJ, Hamilton TA, Sussman HH:  Comparison of human alkaline phosphatase isoenzymes: Structural evidence for three protein classes . Biochem J 1979;;181:67-73.
13 +
Seargeant LE, Stinson RA:  Evidence that three structural genes code for human alkaline phosphatases . Nature 1979;;281:152-154.
14 +
Harris H:  Multilocus enzyme systems and the evolution of gene expression: The alkaline phosphatases as a model example . Harvey Lect 1980;-1981;76:95-124.
15 +
Mulivor RA, Plotkin LI, Harris H:  Differential inhibition of the products of the human alkaline phosphatase loci . Ann Hum Genet 1978;;42:1-13.
16 +
Robison R:  The possible significance of hexosephosphoric esters in ossification . Biochem J 1923;;7:286-293.
17 +
Whyte MP, Vrabel LA:  Infantile hypophosphatasia fibroblasts proliferate normally in culture: Evidence against a role for alkaline phosphatase (tissue nonspecific isoenzyme) in the regulation of cell growth and differentiation . Calcif Tissue Int 1987;;40:1-7.
18 +
Posen S, Lee C, Vines R, et al:  Transient hyperphosphatasemia of infancy—an insufficiently recognized syndrome . Clin Chem 1977;;23:292-294.
19 +
Bayer PM, Hotschek H, Knoth E:  Intestinal alkaline phosphatase and the ABO blood group systems—a new aspect . Clin Chem Acta 1980;;108:81-87.
20 +
Epstein E, Kiechle FL, Artiss JD, et al:  The clinical use of alkaline phosphatase enzymes . Clin Lab Med 1986;;6:491-505.
21 +
Griffin CA, Smith M, Henthorn PS, et al:  Human placental and intestinal alkaline phosphatase genes map to 2q34-q37 . Am J Hum Genet 1987;;41:1025-1034.
22 +
Swallow DM, Povey S, Parkar M, et al:  Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1 . Ann Hum Genet 1986;;50:229-235.
23 +
Wolf PL:  Clinical significance of increased or decreased serum alkaline phosphatase isoenzymes . Clin Lab Med 1986;;6:525-532.
24 +
Low MG, Saltiel AR:  Structural and functional roles of glycosylphosphatidylinositol in membranes . Science 1988;;239:268-275.
25 +
Rubenstein LV, Ward NC, Greenfield S:  In pursuit of the abnormal serum alkaline phosphatase: A clinical dilemma . J Gen Intern Med 1986;;1:38-43.
26 +
Turnbull JM, Buck C:  The value of preoperative screening investigations in otherwise healthy individuals . Arch Intern Med 1987;;147:1101-1105.
27 +
Cebul RD, Beck JR:  Biochemical profiles: Applications in ambulatory screening and preadmission testing of adults . Ann Intern Med 1987;;106: 403-413.

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1 +
McComb RB, Bowers GN Jr, Posen S: Alkaline Phosphatase . New York, Plenum Press, 1979;.
2 +
Wilson JW:  Inherited elevation of alkaline phosphatase activity in the absence of disease . N Engl J Med 1979;;301:983-984.
3 +
Parker PH, Ghishan FK:  Asymptomatic familial elevation of serum alkaline phosphatase levels . AJDC 1980;;134:1094-1095.
4 +
McEvoy M, Skrabanek P, Wright E, et al:  Family with raised serum alkaline phosphatase activity in the absence of disease . Br Med J 1981;;282:1272.
5 +
Ducobu J, Dupont P:  Inherited raised alkaline phosphatase activity in the absence of disease . Lancet 1981;;1:1372-1373.
6 +
Nogueras LC, Lleida JV, Badia MS, et al:  Raised serum alkaline phosphatase activity in one family . Arch Intern Med 1982;;142:188-189.
7 +
Kruse K:  Inherited isolated hyperphosphatasemia . Acta Pediatr Scand 1983;;72:833-835.
8 +
Rico H, Martinez F, Romero P, et al:  Benign familial hyperphosphatasemia: A case report . Rev Clin Esp 1987;;180:465-466.
9 +
Mulivor RA, Boccelli D, Harris H:  Quantitative analysis of alkaline phosphatases in serum and amniotic fluid: Comparison of biochemical and immunologic assays . J Lab Clin Med 1985;;105:342-348.
10 +
Shephard MDS, Peake MJ:  Quantitative method for determining serum alkaline phosphatase isoenzyme activity: I. Guanidine hydrochloride: New reagent for selectively inhibiting major serum isoenzymes of alkaline phosphatase . J Clin Pathol 1986;;39:1025-1030.
11 +
Mulivor RA, Hannig VL, Harris H:  Developmental changes in human intestinal alkaline phosphatase . Proc Natl Acad Sci USA 1978;;75:3909-3912.
12 +
McKenna MJ, Hamilton TA, Sussman HH:  Comparison of human alkaline phosphatase isoenzymes: Structural evidence for three protein classes . Biochem J 1979;;181:67-73.
13 +
Seargeant LE, Stinson RA:  Evidence that three structural genes code for human alkaline phosphatases . Nature 1979;;281:152-154.
14 +
Harris H:  Multilocus enzyme systems and the evolution of gene expression: The alkaline phosphatases as a model example . Harvey Lect 1980;-1981;76:95-124.
15 +
Mulivor RA, Plotkin LI, Harris H:  Differential inhibition of the products of the human alkaline phosphatase loci . Ann Hum Genet 1978;;42:1-13.
16 +
Robison R:  The possible significance of hexosephosphoric esters in ossification . Biochem J 1923;;7:286-293.
17 +
Whyte MP, Vrabel LA:  Infantile hypophosphatasia fibroblasts proliferate normally in culture: Evidence against a role for alkaline phosphatase (tissue nonspecific isoenzyme) in the regulation of cell growth and differentiation . Calcif Tissue Int 1987;;40:1-7.
18 +
Posen S, Lee C, Vines R, et al:  Transient hyperphosphatasemia of infancy—an insufficiently recognized syndrome . Clin Chem 1977;;23:292-294.
19 +
Bayer PM, Hotschek H, Knoth E:  Intestinal alkaline phosphatase and the ABO blood group systems—a new aspect . Clin Chem Acta 1980;;108:81-87.
20 +
Epstein E, Kiechle FL, Artiss JD, et al:  The clinical use of alkaline phosphatase enzymes . Clin Lab Med 1986;;6:491-505.
21 +
Griffin CA, Smith M, Henthorn PS, et al:  Human placental and intestinal alkaline phosphatase genes map to 2q34-q37 . Am J Hum Genet 1987;;41:1025-1034.
22 +
Swallow DM, Povey S, Parkar M, et al:  Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1 . Ann Hum Genet 1986;;50:229-235.
23 +
Wolf PL:  Clinical significance of increased or decreased serum alkaline phosphatase isoenzymes . Clin Lab Med 1986;;6:525-532.
24 +
Low MG, Saltiel AR:  Structural and functional roles of glycosylphosphatidylinositol in membranes . Science 1988;;239:268-275.
25 +
Rubenstein LV, Ward NC, Greenfield S:  In pursuit of the abnormal serum alkaline phosphatase: A clinical dilemma . J Gen Intern Med 1986;;1:38-43.
26 +
Turnbull JM, Buck C:  The value of preoperative screening investigations in otherwise healthy individuals . Arch Intern Med 1987;;147:1101-1105.
27 +
Cebul RD, Beck JR:  Biochemical profiles: Applications in ambulatory screening and preadmission testing of adults . Ann Intern Med 1987;;106: 403-413.

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