Advances in Diagnosis of Biochemical Disorders

  • H. Galjaard


At present some 4500 disorders in man are known or assumed to be of Mendelian inheritance. Most of the genetic disorders have initially been defined by clinicians on the basis of clinical and pathological manifestations [1–3]. The development of chromatographic methods in the 1950s stimulated the use of chemical analyses in the diagnosis of genetic disorders and led to an exponential discovery rate of hereditary amino acidopathies during the 1960s. The important work on normal and abnormal haemoglobins by Pauling, Ingram and others led the way to the search for the responsible (enzyme) protein defects in other genetic diseases and during the past three decades nearly 400 genetic protein defects have been identified. This has offered new perspectives in health care and in basic research.


Chorionic Villus Lysosomal Storage Disorder Purine Nucleoside Phosphorylase Fetal Abnormality Antenatal Diagnosis 
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  1. 1.
    McKusick VA. Mendelian inheritance in man, 8th edn. Baltimore: Johns Hopkins University Press, 1988.Google Scholar
  2. 2.
    Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease, 6th edn. New York: McGraw Hill, 1989.Google Scholar
  3. 3.
    Galjaard H. Genetic metabolic disease: early diagnosis and prenatal analysis. Amsterdam: Elsevier, 1980.Google Scholar
  4. 4.
    Benson PF. Screening and management of potentially treatable genetic metabolic disorders. Lancaster: MTP Press, 1984.CrossRefGoogle Scholar
  5. 5.
    Bickel H, Guthrie R, Hammersen, eds. Neonatal screening for inborn errors of metabolism. Berlin: Springer, 1980.Google Scholar
  6. 6.
    Kaback MM, ed. Tay-Sachs disease: screening and prevention. New York: Alan Liss, 1977.Google Scholar
  7. 7.
    Kaback MM. Heterozygote screening. In: Emery AEH, Rimoin D, eds. Principles and practice of medical genetics. Edinburgh: Churchill Livingstone, 1990.Google Scholar
  8. 8.
    Cao A. Results of programmes for antenatal detection of thalassemia in reducing the incidence of the disorder. Blood Rev 1987; 1:169–76.PubMedCrossRefGoogle Scholar
  9. 9.
    WHO report. Community control of hereditary anemias. Bull WHO 1983; 61:63–80.Google Scholar
  10. 10.
    Harper PS. Practical genetic counselling, 2nd edn. Bristol: Wright, 1984.Google Scholar
  11. 11.
    Brambati BM, Simoni G, Fabro S, eds. Chorionic villus sampling. Clinical and biochemical analysis. Vol. 21. New York: Marcel Dekker, 1986.Google Scholar
  12. 12.
    Galjaard H. Fetal diagnosis of inborn errors of metabolism. In: Rodeck CH, ed. Fetal diagnosis of genetic disease. Baillières Clin Obstet Gynaecol 1987; 1:547–68.Google Scholar
  13. 13.
    Kleijer WJ. Prenatal diagnosis. In: Fernandez J, Saudubray JM, Tada K, eds. Inborn metabolic diseases. Berlin: Springer, 1990; 683–95.Google Scholar
  14. 14.
    Galjaard H. World-wide experience with first-trimester fetal diagnosis by molecular analysis. In: Vogel F, Sperling K, eds. Human genetics. Berlin: Springer, 1987; 611–21.Google Scholar
  15. 15.
    Poenaru L. First-trimester prenatal diagnosis of metabolic diseases: a survey in countries from the European Community. Prenat Diagn 1987; 7:331–41.CrossRefGoogle Scholar
  16. 16.
    Galjaard H, Reuser AJJ. Genetic aspects of lysosomal storage disease. In: Dingle JT, Dean RT, Sly W, eds. Lysosomes in biology and pathology. Amsterdam: Elsevier, 1984; 315–46.Google Scholar
  17. 17.
    Human Gene Mapping 9.5. Cytogenet Cell Genet 1988; 49:1–258.CrossRefGoogle Scholar
  18. 18.
    Desnick R. Treatment of inherited metabolic diseases. In: Emery AEH, Rimoin D, eds. Principles of medical genetics. Edinburgh: Churchill Livingstone, 1990.Google Scholar
  19. 19.
    Hasilik A, Neufeld EF. Biosynthesis of lysosomal enzymes in fibroblasts. J Biol Chem 1980; 255:4937–45.PubMedGoogle Scholar
  20. 20.
    Barranger J, Brady RO, eds. Molecular basis of lysosomal storage disorder. New York: Academic Press, 1984.Google Scholar
  21. 21.
    Cooper DN, Schmidtke J. Diagnosis of genetic disease using recombinant DNA, 2nd edn. Hum Genet 1989; 83:307–34.PubMedCrossRefGoogle Scholar
  22. 22.
    Bremer HJ, Duran M, Kamerling JP, Przyrembel H, Wadman S. Disturbance of amino acid metabolism: clinical chemistry and diagnosis. Munich: Urban and Schwarzenberg, 1981.Google Scholar
  23. 23.
    Goodman SI, Markey SP. Diagnosis of organic acidemias by gas chromatography — mass spectrometry. Laboratory and research methods in biology and medicine, vol. 6. New York: Alan Liss, 1981.Google Scholar
  24. 24.
    Galjaard H. Miniaturisation of biochemical analysis of cultured (amniotic fluid) cells. In: Latt SA, Darlington GJ, eds. Methods in cell biology, vol. 26. New York: Academic Press, 1982; 241–68.Google Scholar
  25. 25.
    Kleijer WJ, Thoomes R, Galjaard H, Wendel U, Fowler B. First-trimester (chorion biopsy) diagnosis of citrullinaemia and methylmalonic aciduria. Lancet 1984; ii:1340.Google Scholar
  26. 26.
    Kleijer WJ, Horsman D, Mancini GMS, Fois A, Boué J. First-trimester diagnosis of maple syrup urine disease on intact chorionic villi. N Engl J Med 1985; 313:1608.PubMedGoogle Scholar
  27. 27.
    Rodeck CH, Nicolaides KH. Fetoscopy and fetal tissue sampling. Br Med Bull 1987; 39:332–7.Google Scholar
  28. 28.
    Golbus HS, Simpson TJ, Koresawa M, Appelman Z, Ropers C. The prenatal determination of glucose-6 phosphatase activity by fetal liver biopsy. Prenat Diagn 1988; 8:101–4.CrossRefGoogle Scholar
  29. 29.
    Danpure CJ, Jennings PR, Penketh RJ, Wise PJ, Cooper PJ, Rodeck CH. Fetal liver alanine: glyoxylate amino transferase and the prenatal diagnosis of primary hyperoxaluria type 1. Prenat Diagn 1989; 9:271–81.PubMedCrossRefGoogle Scholar
  30. 30.
    Status report on fetoscopy and fetal tissue sampling. Prenat Diagn 1984; 4:79–81.CrossRefGoogle Scholar
  31. 31.
    Epstein CJ, Cox DR, Schonberg SA, Hogge WA. Recent developments in the prenatal diagnosis of genetic diseases and birth defects. Ann Rev Genet 1983; 17:49–83.PubMedCrossRefGoogle Scholar
  32. 32.
    Weiner CP. The role of cordocentesis in fetal diagnosis. In: Williamson RA, ed. Fetal diagnosis. Clin Obstet Gynaecol 1988; 31:285–92.Google Scholar
  33. 33.
    Nicolaides KH, Rodeck CH. Fetal blood sampling. In: Rodeck CH, ed. Fetal diagnosis of genetic defects. Baillières Clin Obstet Gynaecol 1987; 623–48.Google Scholar
  34. 34.
    Shapiro LJ, Aleck KA, Kaback MM et al. Metachromatic leucodystrophy without arylsulfatase A deficiency. Pediat Res 1979; 13:1179–81.PubMedCrossRefGoogle Scholar
  35. 35.
    Mancini GMS, Hoogeveen AT, Galjaard H, Mansson JE, Svennerholm S. Ganglioside GM1 metabolism in living human fibroblasts with β-galactosidase deficiency. Hum Genet 1986; 73:35–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Weatherall DJ, Clegg JB. The thalassemia syndromes, 2nd edn. Oxford: Blackwell, 1981.Google Scholar
  37. 37.
    Reuser AJJ, Kroos M, Willemsen R, Swallow D, Tager JM, Galjaard H. Clinical diversity in glycogenosis II: biosynthesis and in situ localization of acid α-glucosidase in mutant fibroblasts. J Clin Invest 1987; 79:1689–99.PubMedCrossRefGoogle Scholar
  38. 38.
    Sandhoff K, Conzelmann E, Neufeld EF, Kaback MM, Suzuki K. The GM2-gangliosidosis. In: Scriver CR, Beaudete AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease, 6th edn. New York: McGraw Hill, 1989; 1807–39.Google Scholar
  39. 39.
    Wenger DA, Tarby TJ, Wharton C. Macular cherry-red spots and myoclonus with dementia: coexistent neuraminidase and β-glactosidase deficiences. Biochem Biophys Res Commun 1978; 82:589–95.PubMedCrossRefGoogle Scholar
  40. 40.
    Leroy JG, Ho MW, McBrinn MC, Zeelke K, Jacob J, O’Brien JS. I-cell disease: biochemical studies. Pediat Res 1972; 6:752–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Robinson BH. Lactic acidemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease, 6th edn. New York: McGraw Hill, 1989; 869–88.Google Scholar
  42. 42.
    Hasilik A, Neufeld EF. Biosynthesis of lysosomal enzymes in fibroblasts: synthesis as precursors of higher molecular weight. J Biol Chem 1980; 255:4937–45.PubMedGoogle Scholar
  43. 43.
    Dingle JT, Dean RT, Sly W, eds. Lysosomes in biology and pathology. Amsterdam: Elsevier, 1984.Google Scholar
  44. 44.
    Barranger J, Brady RO, eds. Molecular basis of lysosomal storage disorders. New York: Academic Press, 1984.Google Scholar
  45. 45.
    d’Azzo A, Hoogeveen AT, Reuser AJJ, Robinson D, Galjaard H. Molecular defect in combined ß-galactosidase and neuraminidase deficiency. Proc Natl Acad Sci 1982; 79:4535–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Hoogeveen AT, Verheijen FW, Galjaard H. The relation between human lysosomal ß-galactosidase and its protective protein. J Biol Chem 1983; 258:12143–6.PubMedGoogle Scholar
  47. 47.
    Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H. Human placental neuraminidase. Am J. Biochem 1985; 149:315–21.Google Scholar
  48. 48.
    Galjart NJ, Gillemans CHAM, Harris A et al. Expression of cDNA encoding the human protective protein associated wth lysomal ß-galactosidase and neuraminidase: homology to yeast proteases. Cell 1988; 54:755–64.PubMedCrossRefGoogle Scholar
  49. 49.
    Li YT, Li SC. Activator proteins related to the hydrolysis of glycosphingolipids catalyzed by lysosomal glycosidases. In: Dingle JT, Dean RT, Sly W, eds. Lysosomes in biology and pathology. Amsterdam: Elsevier, 1984; 99–118.Google Scholar
  50. 50.
    O’Brien JS, Kretz KA, Dewjyu N, Wenger DA, Esch F, Fluharty AL. Coding of two sphingolipid activator proteins by the same genetic locus. Science 1988; 241:1091–101.Google Scholar
  51. 51.
    Nakano T, Sandhoff K, Stümper J, Christomanou H, Suzuki K. Structure of full-length cDNA encoding for sulfatide activator. J Biochem 1989; 105:152–4.PubMedGoogle Scholar
  52. 52.
    Diggelen OP van, Schindler, D, Willemsen R et al. α-N-acetylgalactosaminidase deficiency: a new lysosomal storage disorder. J Inherited Metab Dis 1988; 11:349–57.PubMedCrossRefGoogle Scholar
  53. 53.
    Gahl W, Baskan N, Tietze F, Bernardini I, Schulman JD. Cystine transport is defective in isolated leukocyte lysosomes in patients with cystinosis. Science 1982; 217:1263–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Mancini GMS, Jong HR de, Galjaard H, Verheijen FW. Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane: evidence for a group-specific transport system for acidic monosaccharides. J Biol Chem 1989; 264: 15247–54.PubMedGoogle Scholar
  55. 55.
    Weatherall DJ. The new genetics and clinical practice, 3rd edn. Oxford: Oxford University Press, 1990.Google Scholar

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© Springer-Verlag London Limited 1991

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  • H. Galjaard

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