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Adult hypophosphatasia without apparent skeletal disease: “odontohypophosphatasia“ in four heterozygote members of a family

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Summary

Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient.

Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase.

The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered.

The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogenous disorder which includes both severe and clinically mild forms.

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References

  1. Anderton JM (1979) Orthopaedic problems in adult hypophosphatasia. A report of 2 cases. J Bone Joint Surg 61 B:82–84

    Google Scholar 

  2. Beisel WR, Austen KF, Rosen H, Herndon EG (1969) Metabolic observations in adult hypophosphatasia. Am J Med 29:369–376

    Google Scholar 

  3. Bethune JE, Dent CE (1960) Hypophosphatasia in the adult. Am J Med 28:615–622

    Google Scholar 

  4. Birtwell WM, Riggs L, Peterson LFA, Jones JD (1967) Hypophosphatasia in an adult. Arch Intern Med 120:90–93

    Google Scholar 

  5. Bixler D, Poland C, Brandt IK, Nicholas NJ (1974) Autosomal dominant hypophosphatasia without skeletal disease. Am J Hum Genet 26:14A

    Google Scholar 

  6. Danovitch SH, Baer PN, Laster L (1968) Intestinal alkaline phosphatase activity in familial hypophosphatasia. N Engl J Med 278:1253–1260

    Google Scholar 

  7. Eaton RH, Moss DW (1967) Alkaline orthophosphatase and inorganic pyrophosphatase activities in human sera. Nature 214:842–843

    Google Scholar 

  8. Eisenberg E, Pimstone B (1967) Hypophosphatasia in an adult. Clin Orthop 52:199–212

    Google Scholar 

  9. Fishman L, Inglis NR, Fishman WH (1972) Preparation and characterization of human alkaline phosphatase antigens. Clin Chim Acta 38:75–83

    Google Scholar 

  10. Fishman WH, Ghosh NK (1967) Isoenzymes of human alkaline phosphatase. Adv Clin Chem 10:255–371

    Google Scholar 

  11. Fishman WH, Sie HG (1971) Organ specific inhibition of human alkaline phosphatase isoenzymes of liver, bone, intestine and placenta.l-phenylalanine,l-tryptophan andl-homoarginin. Enzymologica 41:141–167

    Google Scholar 

  12. Fishman WH (1974) Perspectives on alkaline phosphatase isoenzymes. Am J Med 56:617–650

    Google Scholar 

  13. Fraser D (1957) Hypophosphatasia. Am J Med 22:730–746

    Google Scholar 

  14. Ghosh NK, Fishman WH (1966) On the mechanism of inhibition of intestinal alkaline phosphatase byl-phenylalanine. J Biol Chem 241:2516–2522

    Google Scholar 

  15. Goldfischer S, Johnson AB, Morecki R (1976) Hypophosphatasia. A cytochemical study of phosphatase activities. Lab Invest 35:55–62

    Google Scholar 

  16. Hartenfels S (1982) Adulte Hypophosphatasie — eine Familienuntersuchung. Inaugural-Dissertation, Justus-Liebig Universität Gießen

  17. Hørder M (1972) Colorimetric determination of orthophosphate in the assay of inorganic pyrophosphatase activity. Anal Biochem 49:37–47

    Google Scholar 

  18. Hørder M (1972) Inorganic pyrophosphatase activity in human sera with elevated alkaline orthophosphatase. Clin Chim Acta 42:373–381

    Google Scholar 

  19. Hørder M (1973) The inorganic pyrophosphatase activity associated with forms of alkaline phosphatase isolated from human serum. Clin Chim Acta 49:383–388

    Google Scholar 

  20. Hosenfeld D, Hosenfeld A (1973) Qualitative and quantitative Untersuchung der Isoenzyme der alkalischen Serumphosphatase bei der Hypophosphatasie. Klin Paediatr 185:437–443

    Google Scholar 

  21. Jardon OM, Burney DW, Fink RL (1970) Hypophosphatasia in an adult. J Bone Joint Surg 52A:1477–1484

    Google Scholar 

  22. Jedrychowski JR, Duperon D (1979) Childhood hypophosphatasia with oral manifestations. J Oral Med 34:18–22

    Google Scholar 

  23. Justus J, Rupprecht E, Recknagel R, Justus B (1974) Morphologischer und klinischer Beitrag zur Hypophosphatasia congenita letalis. Kinderaerztl Prax 42:148–155

    Google Scholar 

  24. Käbisch A (1982) Quantitative Bestimmung von Phosphoäthanolamin im Urin von gesunden Probanden und Mitgliedern einer Familie mit adulter Hypophosphatasie. Inaugural-Dissertation, Justus-Liebig Universität Gießen

    Google Scholar 

  25. Kousseff BG, Mulivor RA (1981) Prenatal diagnosis of hypophosphatasia. Obstet Gynecol [suppl] 57:9S-12S

    Google Scholar 

  26. Licata AA, Radfar N, Bartfer FC, Bou E (1978) The urinary excretion of phosphoethanolamine in diseases other than hypophosphatasia. Am J Med 64:133–138

    Google Scholar 

  27. Mc Cance RA, Fairweather DV, Barrett AM, Morrison AB (1956) Genetic, clinical, biochemical and pathological features of hypophosphatasia. Q J Med 25:523–537

    Google Scholar 

  28. Méhes K, Klujber L, Lassu G, Kajtár P (1972) Hypophosphatasia: Screening and family investigations in an endogamous Hungarian village. Clin Genet 3:60–66

    Google Scholar 

  29. Merker H, Heilmeyer L (1960) Die alkalische Phosphatase neutrophiler Leukozyten. Zytochemischer Nachweis und Aktivität bei Erkrankungen und Reaktionen des blutbildenden Systems. Dtsch Med Wochenschr 85:253–259

    Google Scholar 

  30. Millán JL, Whyte MP, Avioli LV, Fishman WH (1980) Hypophosphatasia (adult form): Quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. Clin Chem 26:840–845

    Google Scholar 

  31. O'Duffy JD (1970) Hypophosphatasia associated with calcium pyrophosphate dihydrate deposits in cartilage. Arthritis Rheum 13:381–388

    Google Scholar 

  32. Paolaggi J-B, Job C, Durigon M, Alterescu R, Auquier L (1978) Hypophosphatasie de l'adulte à manifestations cliniques tardives. Nouv Presse Med 7:4285–4289

    Google Scholar 

  33. Pimstone B, Eisenberg E, Silverman S (1966) Hypophosphatasia: Genetic and dental studies. Ann Intern Med 65:722–729

    Google Scholar 

  34. Rasmussen H, Bartter FC (1978) Hypophosphatasia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease, chap 55. Mc Graw-Hill, New York, p 1340

    Google Scholar 

  35. Rasmussen K (1968) Phosphorylethanolamine and hypophosphatasia. Dan Med Bull 15:1–85

    Google Scholar 

  36. Rick W, Hausamen T-U (1974) Kinetischer Test: alkalische Phosphatase. In: Klinisches Labor, 12 edn. Merck, Darmstadt, p 207

    Google Scholar 

  37. Robinson JC, Pierce JE (1964) Differential action of neuraminidase on human serum alkaline phosphatases. Nature 204:472–473

    Google Scholar 

  38. Sørensen E, Flodgaard H (1975) Adult hypophosphatasia. Acta Med Scand 197:357–360

    Google Scholar 

  39. Sørensen SA, Flodgaard H, Sørensen E (1978) Serum alkaline phosphatase, phosphorylethanolamine and inorganic phosphate in plasma and urine. A genetic and clinical study of hypophosphatasia. Monogr Hum Genet 10:66–69

    Google Scholar 

  40. Warshaw JB, Littlefield JW, Fishman WH, Inglis NR, Stolbach LL (1971) Serum alkaline phosphatase in hypophosphatasia. J Clin Invest 50:2137–2142

    Google Scholar 

  41. Weinstein S, Whyte MP (1981) Heterogeneity of adult hypophosphatasia. Arch Intern Med 141:727–731

    Google Scholar 

  42. Whyte MP, Teitelbaum SL, Murphy WA, Bergfeld MA, Avioli LV (1979) Adult hypophosphatasia. Clinical, laboratory and genetic investigation of a large kindred with review of the literature. Medicine 58:329–347

    Google Scholar 

  43. Whyte MP, Murphy WA, Fallon MD (1982) Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasia in a large Oklahoma kindred. Am J Med 72:631–641

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik der Universität Marburg, Germany

    F. Eberle

  2. Zentrum für Innere Medizin der Universität Gießen, Germany

    H. Pralle & A. Käbisch

  3. Abt. für Anaesthesiologie und Intensivmedizin der Universität Gießen, Germany

    S. Hartenfels

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  1. F. Eberle
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  2. S. Hartenfels
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  3. H. Pralle
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  4. A. Käbisch
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Eberle, F., Hartenfels, S., Pralle, H. et al. Adult hypophosphatasia without apparent skeletal disease: “odontohypophosphatasia“ in four heterozygote members of a family. Klin Wochenschr 62, 371–376 (1984). https://doi.org/10.1007/BF01716257

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  • DOI: https://doi.org/10.1007/BF01716257

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