Genetics of Vitamin-D-Resistant Rickets

  • J. Edward Spence
  • Gad Kainer
  • James C. M. Chan
Part of the Topics in Renal Medicine book series (TIRM, volume 9)

Abstract

Vitamin-D-resistant rickets (VDRR) is a term used to describe several different genetic disorders of phosphate and vitamin D metabolism that are refractory to the treatment regimen used for vitamin-D-deficiency rickets. Thirty years ago it was felt that all cases of VDRR were due to a single X-linked genetic disorder [1, 2]. Because hypophosphatemia was a prominent feature, the disease was called either X-linked hypophosphatemia (XLH) or familial hypophosphatemia (McKusick catalogue, MIM 30780). While XLH continues to account for the majority of VDRR cases, since 1960 there have been numerous reports of non-X-linked VDRR, including both autosomal dominant [3] and autosomal recessive [4, 5] forms. In addition, two human X-linked genes that may be implicated in VDRR have been described [6]. These findings indicate that the genetic regulation of renal phosphate transport is more complicated than was thought previously [7, 8]. The purpose of this chapter is to review the mode of inheritance of various forms of VDRR. The emphasis will be placed on XLH, which is the best-characterized condition of this group.

Keywords

Recombination Calcitonin Mandel Retinitis Rickets 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Winters RW, Graham JB, Williams TF, McFalls, VW, Burnett CH: A genetic study of familial hypophosphatemia and vitamin D resistant rickets. Trans Assoc Am Physicians 70:234–242, 1957.PubMedGoogle Scholar
  2. 2.
    Graham JB, McFalls VW, Winters RW: Familial hypophosphatemia with vitamin D-resistant rickets. II: Three additional kindreds of the sex-linked dominant type with a genetic analysis of four such families. Am J Hum Genet 11:311–332, 1959.PubMedGoogle Scholar
  3. 3.
    Scriver CR, MacDonald W, Reade T, Glorieux FH, Nogrady B: Hypophosphatemic nonrachitic bone disease: An entity distinct from X-linked hypophosphatemia in the renal defect, bone involvement, and inheritance. Am J Med Genet 1:101–117, 1977.PubMedCrossRefGoogle Scholar
  4. 4.
    Stamp TCB, Baker LRI: Recessive hypophosphataemic rickets, and possible aetiology of the “vitamin D-resistant” syndrome. Arch Dis Child 51:360–365, 1976.PubMedCrossRefGoogle Scholar
  5. 5.
    Tieder M, Modai D, Shaked U, Samuel R, Arie R, Halabe A, Maor J, Weissgarten J, Averbukh Z, Cohen N, Edelstein S, Liberman UA: “Idiopathic” hypercalciuria and hereditary hypophosphatemic rickets: two phenotypical expression of a common genetic defect. N Engl J Med 316:125–129, 1987.PubMedCrossRefGoogle Scholar
  6. 6.
    Boneh A, Reade TM, Scriver CR, Rishikof E: Audiometrie evidence for two forms of X-linked hypophosphatemia in humans, apparent counterparts of Hyp and Gy mutations in mouse. Am J Med Genet 27:997–1003, 1987.PubMedCrossRefGoogle Scholar
  7. 7.
    Scriver CR, Reade TM: Renal hypophosphataemia has several mendelian forms (letter). Lancet ii:918, 1987.CrossRefGoogle Scholar
  8. 8.
    Smith R, O’Riordan JLH: Of mouse and man: the hypophosphataemic genes. Q J Med 64:705–707, 1987.PubMedGoogle Scholar
  9. 9.
    Mellanby E: An experimental investigation on rickets. Lancet i:407–412, 1919.Google Scholar
  10. 10.
    McCollum EV, Simmonds N, Becker JE, Shipley PG: Studies on experimental rickets. XXI. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J Biol Chem 53:293–312, 1922.Google Scholar
  11. 11.
    Albright F, Butler AM, Bloomberg E: Rickets resistant to vitamin D therapy. Am J Dis Child 54:529–547, 1937.Google Scholar
  12. 12a.
    Christensen JF: Three familial cases of atypical late rickets. Acta Paediatr Scand 28:247–270, 1940CrossRefGoogle Scholar
  13. 12b.
    Christensen JF: Three familial cases of atypical late rickets. Acta Paediatr Scand 28:247–270, 1941.CrossRefGoogle Scholar
  14. 13.
    Winters RW, Graham JB, Williams TF, McFalls VW, Burnett CH: A genetic study of familial hypophosphatemia and vitamin D resistant rickets with a review of the literature. Medicine 37:97–142, 1958.PubMedCrossRefGoogle Scholar
  15. 14.
    Burnett CH, Dent CE, Harper C, Warland BJ: Vitamin D-resistant rickets: Analysis of twenty-four pedigrees with hereditary and sporadic cases. Am J Med 36:222–232, 1964.PubMedCrossRefGoogle Scholar
  16. 15.
    Winters RW, McFalls VW, Graham JB: “Sporadic” hypophosphatemia and vitamin D-resistant rickets: Report of a case. Pediatrics 25:959–966, 1960.PubMedGoogle Scholar
  17. 16.
    Rasmussen H, Anast C: Familial hypophosphatemic rickets and vitamin D-dependent rickets. In: Stanbury JB., Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds): The Metabolic Basis of Inherited Disease, 5th ed. New York: McGraw-Hill Book Co., 1983, pp. 1743–1773.Google Scholar
  18. 17.
    Chan JCM, Alon U, Hirschman GM: Renal hypophosphatemic rickets. J Pediatr 106:533–544, 1985.PubMedCrossRefGoogle Scholar
  19. 18.
    Lyon MF: Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet 14:135–148, 1962.PubMedGoogle Scholar
  20. 19.
    Eicher EM, Southard JL, Scriver CR, Glorieux FH: Hypophosphatemia: Mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci USA 73:4667–4671, 1976.PubMedCrossRefGoogle Scholar
  21. 20.
    Meyer RA: X-linked hypophosphatemia (familial or sex-linked vitamin-D-resistant rickets): X-linked hypophosphatemic (Hyp) mice. Am J Pathol 118:340–342, 1985.PubMedGoogle Scholar
  22. 21.
    Tenenhouse HS, Scriver CR, Mclnnes RR, Glorieux FH: Renal handling of phosphate in vivo and in vitro by the X-linked hypophosphatemic male mouse: Evidence for a defect in the brush border membrane. Kidney Int 14:236–244, 1978.PubMedCrossRefGoogle Scholar
  23. 22.
    Fukase M, Avioli LV, Birge SJ, Chase LR: Abnormal regulation of 25-hydroxyvitamin D3-1α-hydroxylase activity by calcium and calcitonin in renal cortex from hypophosphatemic (Hyp) mice. Endocrinology 114:1203–1207, 1984.PubMedCrossRefGoogle Scholar
  24. 23.
    Drezner MK, Lyles KW, Haussler MR, Harrelson JM: Evaluation of a role for 1,25-dihydroxyvitamin D3 in the pathogenesis and treatment of X-linked hypophosphatemic rickets and osteomalacia. J Clin Invest 66:1020–1032, 1980.PubMedCrossRefGoogle Scholar
  25. 24.
    Tenenhouse HS, Henry HL: Protein kinase activity and protein kinase inhibitor in mouse kidney: Effect of the X-linked Hyp mutation and vitamin D status. Endocrinology 117: 1719–1726, 1985.PubMedCrossRefGoogle Scholar
  26. 25.
    Buckle VJ, Edward JH, Evan EP, Jonasson JA, Lyon MF, Peters J, Searle AG: Comparative maps of human and mouse X chromosomes. Cytogenet Cell Genet 40:594–595, 1985.Google Scholar
  27. 26.
    Botstein D, White RL, Skolnick M, Davis RW: Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331, 1980.PubMedGoogle Scholar
  28. 27.
    Read AP, Thakker RV, Davies KE, et al.: Mapping of human X-linked hypophosphataemic rickets by multilocus linkage analysis. Hum Genet 73:267–270, 1986.PubMedCrossRefGoogle Scholar
  29. 28.
    Mächler M, Frey D, Gal A, Orth U, Wienker TF, Fanconi A, Schmid W: X-linked dominant hypophosphatemia is closely linked to DNA markers DXS41 and DXS43 at Xp22. Hum Genet 73:271–275, 1986.PubMedCrossRefGoogle Scholar
  30. 29.
    Davies KE, Mandel J-L, Weissenbach J, Fellous M: Report of the committee on the genetic constitution of the X and Y chromosomes. Cytogenet Cell Genet 46:277–315, 1987.PubMedCrossRefGoogle Scholar
  31. 30.
    Thakker, RV, Read AP, Davies KE, et al.: Bridging markers defining the map position of X-linked hypophosphataemic rickets. J Med Genet 24:756–760, 1987.PubMedCrossRefGoogle Scholar
  32. 31.
    Hoffman EP, Brown RH, Kunkel LM: Dystrophin: The protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928, 1987.PubMedCrossRefGoogle Scholar
  33. 32.
    Lyon MF, Scriver CR, Baker LRI, Tenenhouse HS, Kronick J, Mandla S: The Gy mutation: Another cause of X-linked hypophosphatemia in mouse. Proc Natl Acad Sci USA 83: 4899–4903, 1986.PubMedCrossRefGoogle Scholar
  34. 33.
    Davies M, Kane R, Valentine J: Impaired hearing in X-linked hypophosphataemic (vitamin-D-resistant) osteomalacia. Ann Intern Med 100:230–232, 1984.PubMedGoogle Scholar
  35. 34.
    O’Malley S, Ramsden RT, Latif A, Kane R, Davies M: Electrocochleographic changes in the hearing loss associated with X-linked hypophosphataemic osteomalacia. Acta Otolaryngol 100:13–18, 1985.PubMedCrossRefGoogle Scholar
  36. 35.
    Gusella JF, Wexler NS, Conneally PM, et al.: A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306:234–238, 1983.PubMedCrossRefGoogle Scholar
  37. 36.
    Spence JE, Rosenbloom CL, O’Brien WE, Seilheimer DK, Cole S, Ferrell RE, Stern RC, Beaudet AL: Linkage of DNA markers to cystic fibrosis in 26 families. Am J Hum Genet 39:729–734, 1986.PubMedGoogle Scholar
  38. 37.
    Ohno S: Sex chromosomes and sex-linked genes. In: Labhart A, Mann T, Samuels LT, Zander J (eds): Monographs on Endocrinology. New York: Springer-Verlag, 1967.Google Scholar
  39. 38.
    Cooper DN, Schmidtke J: DNA restriction fragment length polymorphisms and heterozygosity in the human genome. Hum Genet 66:1–16, 1984.PubMedCrossRefGoogle Scholar
  40. 39.
    Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA: Specific cloning of DNA fragments absent from the DNA of a male patient with an X-chromosome deletion. Proc Natl Acad Sci USA 82:4778–4782, 1985.PubMedCrossRefGoogle Scholar
  41. 40.
    Harrison HE: Oncogenous rickets: Possible elaboration by a tumor of a humoral substance inhibiting tubular reabsorption of phosphate. Pediatrics 52:432–434, 1973.PubMedGoogle Scholar
  42. 41.
    Reddy V, Sivakumar B: Magnesium-dependent vitamin-D-resistant rickets. Lancet i:963–965, 1974.CrossRefGoogle Scholar
  43. 42.
    Bianchine JW, Stambler AA, Harrison HE: Familial hypophosphatemic rickets showing autosomal dominant inheritance. Birth Defects 7:287–294, 1971.PubMedGoogle Scholar
  44. 43.
    Brickman AS, Coburn JW, Kurokawa K, Bethune JE, Harrison HE, Norman AW: Actions of 1,25 dihydroxycholecalciferol in patients with hypophosphatemic, vitamin-D resistant rickets. N Engl J Med 289:495–498, 1973.PubMedCrossRefGoogle Scholar
  45. 44.
    Tieder M, Modai D, Samuel R, Arie R, Halabe A, Bab I, Gabizon D, Liberman UA: Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med 312:611–617, 1985.PubMedCrossRefGoogle Scholar
  46. 45.
    Kainer G, Spence JE, Chan JCM: X-linked hypophosphatemia: Characterization of genetic and metabolic defects. Nephron 51:449–453, 1989PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • J. Edward Spence
  • Gad Kainer
  • James C. M. Chan

There are no affiliations available

Personalised recommendations