A Biomedical View of Enzyme Replacement Strategies in Genetic Disease

  • Charles R. Scriver


A nursery rhyme, which some of us learned when we were children brought tinker, tailor, soldier, and sailor together (Opie and Opie, 1951), rather like this volume, where its authors have been convened from many disciplines to describe how the diverse indexes of our individuality—our proteins—can be handled for biomedical purposes. My contribution to the mix is a chapter on strategies about enzyme replacement therapy; other authors provide the tactical details upon which the successful campaign for such treatment will depend.


Enzyme Replacement Therapy Inborn Error Glycogen Storage Disease Maple Syrup Urine Disease Enzyme Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Austin, J. H., 1967, Some recent findings in leukodystrophies and in gargoylism, in: Inborn Disorders of Sphingolipid Metabolism, (S. M. Aronson and B. W. Volk, eds.) p. 359, Pergamon Press, Inc., Oxford.Google Scholar
  2. Baudhuin, P., Hers, H. G., and Leob, H., 1964, An electron microscopic and biochemical study of type II glycogenosis, Lab. Invest. 13:1139.Google Scholar
  3. Bickel, H., Schultze, H. E., Bruter, W., and Gollner, I., 1956, Versuche zur Coeruloplasminsubstitution bei der hepatocerebralen Degeneration (Wilsonsche Krankheit), Kiln. Wochschr. 34:961.Google Scholar
  4. Boyer, S. M., Siggers, D. C., and Krugger, L. J., 1973, Caveat to protein replacement therapy for genetic disease: immunological implications of accurate molecular diagnosis, Lancet 2:654Google Scholar
  5. Brady, R. O., Tallman, J. F., Johnson, W. G., Gal, A. E., Leahy, W. R., Quirk, J. M., and Dekaban, A. S., 1973, Replacement therapy for inherited enzyme deficiency: use of purified ceramidetrihexosi-dase in Fabry’s disease, New Engl. J. Med. 289:9.Google Scholar
  6. Brady, R. O., Penchev, P. G., Gal, A. E., Hebert, S. R., and Dekaban, A. S., 1974, Replacement therapy for inherited enzyme deficiency: use of purified glucocerebrosidase in Gaucher’s disease, New Engl. J. Med. 291:989.Google Scholar
  7. Bunting, P. S., and Laidler, K. J., 1972, Kinetic studies on solid-supported ß-galactosidase. Biochemistry 11:4477.Google Scholar
  8. Canadian Council on Animal Care, Animal Resources Committee, 1976, Index of Vertabrate Stocks for Research in Canada.Google Scholar
  9. Carter, C. O., 1956, Changing patterns in the causes of death at the Hospital for Sick Children, Great Ormond Street Journal 11:65.Google Scholar
  10. Cass, J., 1973, One medicine—human and veterinary, Perspectives Biol. Med. 16:418. Cederholm-Williams, S. A., 1973, Insoluble enzymes—therapeutic potential, in: Treatment of Inborn Errors of Metabolism (J. W. T. Seakins, R. A. Saunders, and C. Toothill, eds.), SSIEM Symposium No. 10, p. 195, Churchill, Livingston, London.Google Scholar
  11. Chang, T. M. S., 1964, Semipermeable microcapsules, Science 146:524.Google Scholar
  12. Chang, T. M. S., 1972, Artificial Cells, Charles C. Thomas Pub., Springfield, Ill.Google Scholar
  13. Chang, T. M. S., and Poznansky, M. J., 1968, Semipermeable microcapsules containing calatase for enzyme replacement in acalatosalmic mice. Nature 218:243.Google Scholar
  14. Chang, T. M. S., Gonda, A., Dirks, J. H., Coffey, J. F., and Lee-Burns, T., 1972, ACAC microcapsule artificial kidney for the long term and short term management of eleven patients with chronic renal failure, Trans. Amer. Soc. Artificial Internal Organs 18:465.Google Scholar
  15. Childs, B., and Der Kaloustian, M., 1968, Genetic heterogeneity, New Engl. J. Med. 279:1205, 1267 Google Scholar
  16. Childs, B., Miller, S. M., and Beam, A. G., 1972, Gene mutation as a cause of human disease, in: Mutagenic Effects of Environmental Contamination, (H. E. Sutton, and M. I. Harris, eds.), p. 3, Academic Press, Inc. New York.Google Scholar
  17. Clarke, J. T. R., Guttman, R. D., Wolfe, L. S., Beaudoin, J. G., and Morehouse, D. D., 1972, Enzyme replacement therapy by renal allotransplantation in Fabry’s disease, New Engl. J. Med. 287:1215Google Scholar
  18. Cornelius, C. E., 1969, Animal models—a neglected medical resource, N. Engl. J. Med. 281:934Google Scholar
  19. Cuatrecasas, P., Wilchek, M., and Anfinsen, C. B., 1968, Selective enzyme purification by affinity chromatography, Proc. Natl. Acad. Sci. U. S. 61:636.Google Scholar
  20. Daloze, P., Delvin, E. D., Glorieux, F. H., Gorman, J., and Bettez, P., 1974, Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A, Clin. Res. 23:739A.Google Scholar
  21. Day, N., and Holmes, L. B., 1973, The incidence of genetic disease in a university hospital population, Amer. J. Human Genet. 25:237.Google Scholar
  22. Dean, M. F., Muir, H., and Benson, P. F., 1973, Mobilization of glycosaminoglycans by plasma infusion in mucopolysaccharidosis type III—two types of response, Nature New Biol. 243:143.Google Scholar
  23. deBarsy, T., Jacquemin, P., van Hoof, F., and Hers, H. G., 1973, Enzyme replacement in Pompe disease: an attempt with purified human acid a-glucosidase, in: Enzyme Therapy in Genetic Diseases, Birth Defects (Original Article Series, Vol. 9) (R. J. Desnick, R. W. Bernlohr, and W. Krivit, eds.), p. 184, The Williams & Wilkins Company, Baltimore.Google Scholar
  24. DeKaban, A. S., Holden, K. R., and Constantopoulos, G., 1972, Effects of fresh plasma or whole blood transfusions on patients with various types of mucopolysaccharidosis, Pediatrics 50:688.Google Scholar
  25. Desnick, R. J., Allen, K. Y., Simmons, R. L., Majarian, J. S., and Krivit, W., 1971, Treatment of Fabry’s disease: correction of the enzymatic deficiency by renal transplantation, J. Lab. Clin. Med. 78:989.Google Scholar
  26. Desnick, R. J., Krivit, W., Synder, P. D., Desnick, S. J., and Sharp, H. L., 1972, Sandhoffs disease: ultrastructural and biochemical studies, in: Sphingolipidoses and Allied Disorders (S. M. Aronson and B. W. Volk, eds.), p. 351, Plenum Press, New York.Google Scholar
  27. Desnick, R.J., Simmons, R. L., Allen, K. Y., Woods, J. E., Anderson, C. F., Najarian, J. S., and Krmit, W., 1972, Correction of enzymatic deficiencies by renal transplantation: Fabry’s Disease, Surgery 72: 203.Google Scholar
  28. Desnick, R. J., Krivit, W., and Fiddler, M. B., 1975a, Enzyme Therapy in Genetic Diseases: Progress, Principles and Prospects, in: The Prevention of Genetic Disease and Mental Retardation (A. Milunsky, ed.), p. 317, W. B. Saunders. Philadelphia.Google Scholar
  29. Desnick, R. J., Thorpe, S. R., Steger, L., Dullum, D., Cumming, D., and Fiddler, M., 1975b, Enzyme replacement therapy: in vivo fate of nature, erythrocyte and liposome entrapped ß-glucuronidase, Pediat. Res. 9:312.Google Scholar
  30. DiFerrante, N., Nichols, B. L., Donnelly, P. V., Neri, G., Hrgovcic, R., and Berglund, R. K., 1971, Induced degradation of glycosaminoglycans in Hurler’s and Hunter’s syndromes by plasma infusion, Prot Natl. Acad. Sci. U.S. 68:303.Google Scholar
  31. Dumond, D. E., 1975, The limitation of human population: a natural history, Science 187:713Google Scholar
  32. Earley, K., 1975, Disinheriting disease in “The Sciences” N. Y. Acad. Sci. 15(5):19. Google Scholar
  33. Erickson, R. P., Sandman, R., van B. Robertson, W., and Epstein, C. J., 1972, Inefficacy of fresh frozen plasma therapy of mucopolysaccharidosis II, Pediatrics 50:693.Google Scholar
  34. Farrell, D. F., Baker, H. J., Herndon, R. M., Lindsey, J. R., and McKhann, G. M., 1973, Feline GM, gangliosidosis: biochemical and ultrastructural comparisons with the disease in man, J. Neuropathol. Exptl. Neurol. 32:1.Google Scholar
  35. Feinstein, R. N., Howard, J. B., Braun, J. T., and Seaholm, J. E., 1966, Acatalasemic and hyposemic mouse mutants, Genetics 53: 923.Google Scholar
  36. Fernandes, J., and Hulling, F., 1968, Branching-enzyme-deficiency glycogenosis: studies in therapy, Arch. Disease Childhood 43:347.Google Scholar
  37. Friedman, M., and Byers, S. O., 1948, Observations concerning the causes of the excess excretion of uric acid in the Dalmatian dog, J. Biol. Chem. 175:727.Google Scholar
  38. Garrod, A. E., 1902, The incidence of alcaptonuria: a study in chemical individuality, Lancet 2: 1616.Google Scholar
  39. Giblett, E. R., Anderson, J. E., Cohen, F., Pollara, F., and Meuwissen, H. J., 1972, Adenosine-deaminase deficiency in two patients with severly impaired cellular immunity, Lancet 2:1067.Google Scholar
  40. Gillette, P. N., Peterson, C. M., Lin, Y. S., and Cerami, A., 1974, Sodium cyanate as a potential treatment for sickle cell disease, New Engl. J. Med. 290:654.Google Scholar
  41. Goldman, H., Scriver, C. R., Aaron, K., and Pinsky, L., 1970, Use of dithiothreitol to correct cystine storage in cultured cystinotic fibroblasts, Lancet 1:811.Google Scholar
  42. Goldman, H., DePape-Brigger, D., Delvin, E., and Scriver, C. R., 1974, Long-term use of oral dithiothreitol (DTT) in nephropathic cystinosis, Clin. Res. 22:740A.Google Scholar
  43. Goldstein, L., and Katchalski, E., 1968, Use of water-insoluble enzyme derivatives in biochemical analysis and separation, Z. Fur analyt. Chemie 243:375.Google Scholar
  44. Greene, H. L., Hug, G., and Schubert, W. K., 1969, Metachromatic leucodystrophy: treatment with arylsulfatase-A, Arch. Neurol. 20:147.Google Scholar
  45. Gregoriadis, G., 1973, Molecular Trojan Horses, New Scientist, Dec., p. 890.Google Scholar
  46. Gregoriadis, G., 1974, Structural requirements for the specific uptake of macromolecules and liposomes by target tissues, in: Enzyme therapy in lysosomal storage disease. (J. M. Tager, G. J. M. Hooghwichel, and W. T. H. Daems, eds.), p. 131, North Holland Pub. Co., Amsterdam.Google Scholar
  47. Gregoriadis, G., and Ryman, B. E., 1972a, Fate of protein-containing liposomes injected into rats. An approach to the treatment of storage diseases, Eur. J. Biochem. 24:485.Google Scholar
  48. Gregoriadis, G., and Ryman, B. E., 1972b, Lysosomal localization of ß-fructofuranosidase containing lipcsomes injected into rats. Some implications in the treatment of genetic disorders, Biochem. J. 129:123.Google Scholar
  49. Gregoriadis, G., Leatherwood, P. D., and Ryman, B. E., 1971, Enzyme entrapment in liposomes, FEBS Letters 14:95.Google Scholar
  50. Harris, H., 1968, Molecular basis of hereditary disease, Brit. Med. J. 1:135.Google Scholar
  51. Harris, H., and Hopkinson, D. A., 1972, Average heterozygosity per locus in man: an estimate based on the incidence of enzyme polymorphism, Ann. Human Genet. 36:9.Google Scholar
  52. Hirschhorn, R., 1975, Conversion of human erythrocyte-adenosine deaminase activity to different tissue-specific isozymes: evidence for a common catalytic unit, J. Clin. Invest. 55:661Google Scholar
  53. Hors-Cayla, M. C., Maroteaux, P., and deGrouchy, J., 1968, Fibroblastes en culture au cours de mucopolysaccharidoses: influence du serum sur la métachromasie, Ann. Genetique 11:265Google Scholar
  54. Hsia, Y. E., 1975, Treatment in genetic diseases, in: The Prevention of Genetic Disease and Mental Retardation (A. Milunsky, ed.) p. 277, W. B. Saunders Company, Philadelphia.Google Scholar
  55. Hug, G., and Schubert, W. K., 1967a, Hepatic lysosomes in Pompe’s disease: disappearance during glucosodase administration, J. Clin. Invest. 46:1073.Google Scholar
  56. Hug, G., and Schubert, W. K., 1967h, Lysosomes in type II glycogenosis: changes during administration of extract from Aspergillus niger, J. Cell Biol. 35:C1.Google Scholar
  57. Hug, G., Schubert, W. K., and Chuck, G., 1968, Type II glycogenosis: treatment with extract of Aspergillus niger, Clin. Res. 16:345.Google Scholar
  58. Huijing, F., Waltuck, B. L., and Whelan, W. J., 1973, Alpha-glucosidase administration: experiences in two patients with glycogen storage disease compared with animal experiments, in: Enzyme Therapy in Genetic Diseases, Birth Defects (Original Article Series, Vol. 9) (R. J. Desnick, R. W. Bernlohr, and W. Krivit, eds.), p. 191, The Williams & Wilkins Company, Baltimore.Google Scholar
  59. Ihler, G. M., Glew, R. M., and Schrure, F. W., 1973, Enzyme loading of ervthrocctes, Proc. Nat. Acad. Sci. Wash. 70:2663.Google Scholar
  60. Jensen, M., Bunn, H. F., Halikas, G., Kan, Y. W., and Nathan, D. G., 1973, Effects of cyanate and 2,3diphosphoglycerate on sickling: relationship to oxygeneration, J. Clin. Invest. 52:2542.Google Scholar
  61. Johnson, W. G., Desnick, R. J., Long, D. M., Sharp, H. L., Krivit, W., Brady, B., and Brady, R. O., 1973, Intravenous injection of purified hexosaminidase A into a patient with Tay—Sachs disease, in: Enzyme Therapy in Genetic Diseases, Birth Defects: (Original Article Series, Vol. IX) (R. J. Desnick, R. W. Bernlohr, and W. Krivit, eds.), p. 120, The Williams and Wilkins Co., Baltimore.Google Scholar
  62. Jones, T. C., Rachel, D. B., and Migaki, K., 1973, (eds.), The Registry of Comparative Pathology; Animal Models of Human Disease, Baltimore Information Services, Inc., Baltimore.Google Scholar
  63. Kanfer, J. N., Legler, G., Sullivan, J., Raghavan, S. S., and Mumford, R. A., 1975, The Gaucher mouse, Biochem. Biophys. Res. Commun. 67:85.Google Scholar
  64. Katz, J. J., and Crespi, H. L., 1971, Isotope effects in biological systems, in: Isotope Effects in Chemical Reactions. (C. J. Collins and N. S. Bowman, edti.), p. 286, Van Nostrand Reinhold, New York.Google Scholar
  65. Keightley, R. G., Lawton, A. R., Cooper, M. D., and Yunis, E. J., 1975, Successful fetal liver transplantation in a child with severe combined immunodeficiency, Lancet 2:850.Google Scholar
  66. Knudson, A. G., Jr., DiFerrante, N., and Curtis, J. E., 1971, Effect of leucocyte transfusion in a child with type II mucopolysaccharidosis, Proc. Natl. Acad. Sci. U. S. 68:1738.Google Scholar
  67. Kolodny, E. H., 1973, commentary in: Enzyme Therapy in Genetic Diseases,Birth Defects (Original Article Series, Vol. 9) (R. J. Desnick, R. W. Bernlohr, and W. Krivit, eds.), p. 40, The Williams & Wilkins Company, Baltimore.Google Scholar
  68. Lauer, R. M., Mascarinas, T., Racela, A. S., Diehl, A. M., and Brown, B. I., 1968, Administration of a mixture of fungal glucosidases to a patient with type II glycogenesis (Pompe’s disease), Pediatrics 42:672.Google Scholar
  69. Levy, N. L., Synderman, R., Ladda, R. L., and Lieberman, R., 1973, Cytogenetic engineering in vivo: restoration of biologic complement activity to C5-deficient mice by intravenous inoculation of hybrid cells, Proc. Natl. Acad. Sci. U. S. 70:3125.Google Scholar
  70. Lubin, B. H., Pena, V., Mentzer, W. C., Bymun, E., Bradley, T. B., and Pacher, L., 1975, Dimethyl adipimidate: a new antisickling agent, Proc. Natl. Acad. Sci. U. S. 72:43.Google Scholar
  71. Lush, I. E., 1967, The biochemical genetics of vertebrates except man, in: Frontiers of Biology, Vol. 3, (A. Neuberger, and E. L. Tatum, eds.), p. 118, North-Holland Publishing Co., AmsterdamGoogle Scholar
  72. Mapes, C. A., Anderson, R. L., Sweeley, C. C., Desnick, R.J., and Krivit, W., 1970, Enzyme replacement in Fabry’s disease: an inborn error of metabolism, Science 169:987.Google Scholar
  73. McKusick, V. A., 1975, Mendelian inheritance in man, in: Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes, 4th ed., The Johns Hopkins Press, Baltimore.Google Scholar
  74. Merrifield, R. B., 1967, New approaches to the chemical synthesis of peptides, Recent Progr. Hormone Res. 23:451.Google Scholar
  75. Mosback, K., 1970, Matrix-bound enzymes, Part I: The use of different acrylic copolymers as matrices, Acta Chem. Scand. 24:2084.Google Scholar
  76. Motulsky, A. G., and Boman, H., 1974, Genetics and artherosclerosis, in: Proc. 3rd Int. Symp. Artherosclerosis, Oct. 1973 (G. Schettler, and A. Weizel, eds.), Springer-Verlag, Berlin.Google Scholar
  77. Neckers, D. C., 1975, Solid phase synthesis, J. Chem. Educ. 52:695.Google Scholar
  78. Neufeld, E. F., and Cantz, M. J., 1971, Corrective factors for inborn errors of mucopolysaccharide metabolism, Ann. N. Y. Acad. Sci. 179:580.Google Scholar
  79. Norden, A. G. W., and O’Brien, J. S., 1974, Binding of human liver f3-galactosidases to plant lectins insolubilized on agarose, Biochem. Biophys. Res. Commun. 56:193.Google Scholar
  80. O’Brien, J. S., 1973, Ganglioside Storage Disease, in: Advances in Human Genetics (Vol. 3) (H. Harris and K. Hirschhorn, eds.), p. 39, Plenum Press, New York.Google Scholar
  81. Obrien, J. S., Okada, S., Fillerup, D. L., Veath, M. L., Adornato, B., Brenner, P. H., and LeRoy, J. G., 1971, -1-al —SachsDisease: Prenatal Diagnosis. Science 172:61.Google Scholar
  82. O’Brien, J. S., Miller, A. L., Loverde, A. W., and Veath, M. L., 1973, Sanfilippo disease type B: enzyme replacement and metabolic correction in cultured fibroblasts, Science, 181:753.Google Scholar
  83. Opie, I., and Opie, P., 1951, The Oxford Dictionary of Nursery Rhymes, Oxford University Press, OxfordGoogle Scholar
  84. Paillot, B., Remy, N. H., Thomas, D., and Brown, G.. 1974, Path. Biol. 22:491.Google Scholar
  85. Papahadjopoulos, G. P., and Mayhew, E., 1974, Cellular uptake of cyclic AMP captured within phospho-lipid vesicles and effect on cell-growth behaviors. Biorhim. Biophys. Acta 363:404.Google Scholar
  86. Patel, V. P., Koppang, N., Patel, B., and Zeman, W., 1974, p-phenylenediamine-mediated peroxidase deficiency in English setters with neuronal ceroid-lipofuscinosis, Lab. Invest. 30:366.Google Scholar
  87. Phillips, N. C., Robinson, D., Winchester, B. G., and Jolly, R. D., 1974, Mannosidosis in Angus cattle: the enzymic defect, Biochem. J. 137:363.Google Scholar
  88. Polmar, S. H., Wetzler, E. M., Stern, R. C., and Hirschhorn, R., 1975, Restoration of in vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency, Lancet 2:743.Google Scholar
  89. Philippart, M., Franklin, S. S., and Gordon, A., 1972, Reversal of an inborn sphingolipidosis (Fabrv’s disease) by kidney transplantation, Ann. Intern. Med. 77:195.Google Scholar
  90. Poznansky, M. J., and Chang, T. M. S., 1974, Comparison of the enzyme kinetics and immunological properties of catalase immobilized by microencapsulation and catalase in free solution for enzyme replacement, Biochem. Biophys. Acta 334:103.Google Scholar
  91. Rifkind, R. A., 1966, Destruction of injured red cells in vivo, Amer. J. Med. 41:711.Google Scholar
  92. Roberts, D. F., Chavez, J., and Court, S. D. M., 1970, The genetic component in child mortality, Arch. Disease Childhood 45:33.Google Scholar
  93. Scriver, C. R., 1967, Treatment in medical genetics, in: Proc. 3rd Int. Congr. Human Genetics (Chicago, Sept.) U. F. Crow, and J. V. Neel, eds.), p. 45, The Johns Hopkins Press, Baltimore.Google Scholar
  94. Scriver, C. R., 1969, Treatment of inherited disease: realized and potential, Med. Clin. N. Amer. 53:941Google Scholar
  95. Scriver, C. R., 1971, Mutants: consumers with special needs, Nutr. Rev. 29:155.Google Scholar
  96. Scriver, C. R., 1974, Enzyme therapy and induction in genetic disease: pox or pax, Proc. 4th Int. Birth Defects Conf. (A. G. Motulsky, and W. Lentz, eds.), p. 114, Excerpta Medica ICS 310, AmsterdamGoogle Scholar
  97. Striver, C. R., and Rosenberg, L. E., 1973, Amino Acid Metabolism and Its Disorders, W. B. Saunders Ltd., Philadelphia.Google Scholar
  98. Scriver, C. R., Neal, J. L., Saginur, R., and Clow, A., 1973, The frequency of genetic disease and congenital malformation among patients in a pediatric hospital, Can. Med. Assoc. Journal 108:1111.Google Scholar
  99. Scriver, C. R., Chesney, R. W., and McInnes, R. R., 1976, Genetic aspects of renal tubular transport: diversity and topology of carriers, Kidney Int. 9:149.Google Scholar
  100. Silman, I. H., and Katchalski, E., 1966, Water-insoluble derivatives of enzymes, antigens, and antibodies, Ann. Rev. Biochem. 35:873.Google Scholar
  101. Sly, W. S., Glaser, J. G., Roozen, K., Brot, E., and Stahl, P., 1974, Enzyme replacement studies with ßglucuronidase deficiency, in: Enzyme Therapy in Lysosomal Storage Diseases U. M. Tager, G. J. M. Hooghwinkel, and W. Th. Daims, eds.), p. 288, North-Holland Publishing Co., Amsterdam.Google Scholar
  102. Suzuki, K., Suzuki, Y., and Fletcher, T. F., 1972, Further studies on galactocerebroside ß-galactosidase in globoid cell leukodystrophy, in: Sphingolipids,Sphingolipidoses and Allied Disorders (B. W. Volk and S. M. Aronson, eds.), p. 487, Plenum Press, New York.Google Scholar
  103. Sweeley, C. C., Mapes, C. A., Krivit, W., and Desnick, R. J., 1972, Chemistry and metabolism of glycosphingolipids in Fabry’s disease, in: Sphingolipids, Sphingolipidoses and Allied Disorders (B. W. Volk and S. M. Aronson, eds.), p. 287, Plenum Press, New York.Google Scholar
  104. Synder, P. D. Jr., Wold, F., Bernlohr, R. W., Dullum, C., Desnick, R. J., Krivit, W., and Condie, R. M., 1974, Enzyme therapy II: Purified human a-galactosidase A. Stabilization to heat and protease aggregation by complexing with antibody and by chemical modification, Biochem. Biophys. Acta 350:432.Google Scholar
  105. Thoene, J. C., Oshima R. G., Crawhall, J. C., Olson D. L., and Schneider, J. A., 1976, Cystinosis intracellular cystine depletion by aminothiols in vitro and in vivo. J. Clin. Invest. 58:180Google Scholar
  106. Trimble, B. K., and Doughty, J. H., 1974, The amount of hereditary disease in human populations, Ann. Human Genet. (Land.) 38:199.Google Scholar
  107. Wold, F., 1973, Chemical modification of enzymes, in: Enzyme Therapy in Genetic Diseases, Birth Defects (Original Article Series, Vol. 9) (R. J. Desnick, R. W. Bernlohr, and W. Krivit, eds.), p. 46, The Williams & Wilkins Company, Baltimore.Google Scholar
  108. World Health Organization, 1972, Genetic Disorders: Prevention, Treatment and Rehabilitation, Tech. Rept. SerNo. 497, Geneva.Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Charles R. Scriver
    • 1
    • 2
  1. 1.The deBelle Laboratory for Biochemical Genetics McGill University-Montreal Children’s Hospital Research InstituteCanada
  2. 2.The Medical Research Council Genetics Group, Departments of Pediatrics (Faculty of Medicine) and Biology (Faculty of Science)McGill UniversityMontrealCanada

Personalised recommendations