Summary
The occurrence of severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency in erythrocytes has been reported in 14 patients. Enzyme deficiency may result in early depression of the lymphatic system. ADA is detectable in different tissues by photometric and electrophoretic methods. The gene locus for ADA has been localised on chromosome 20. Studies on the enzyme defect in different forms of primary immunodeficiencies led to the description of a well defined nosological entity. New aspects can be expected in the fields of pathogenesis, prenatal diagnosis, genetic councelling, and possibly therapeutic trials.
Zusammenfassung
Von 14 Patienten mit schwerer kombinierter Immundefizienz (SCID) wurde ein Mangel an Adenosindesaminase (ADA) in den Erythrozyten berichtet. Die unzureichende Entwicklung des lymphatischen Systems ist möglicherweise Folge des Enzymmangels. ADA kann spektralphotometrisch und elektrophoretisch in verschiedenen Geweben nachgewiesen werden. Der Genort für ADA liegt auf Chromosom 20. Untersuchungen des Enzymdefekts bei verschiedenen Formen primärer Immundefizienzen erlauben die Abgrenzung einer genetisch definierten Krankheitseinheit. Für die Klinik ergeben sich neue Aspekte in der Pathogeneseforschung, pränatalen Diagnostik, genetischen Beratung und möglicherweise kausalen Behandlung der SCID mit ADA-Mangel.
Similar content being viewed by others
Literatur
Ackeret, C., Plüss, H.J., Hitzig, W.H.: Hereditary severe combined immunodeficiency and adenosine deaminase deficiency. Ped. Res.10, 67 (1976)
Akedo, H., Nishihara, H., Shinkai, K., Komatsu, K.: Adenosine deaminase of two different molecular sizes in human tissues. Biochim. Biophys. Acta212, 189 (1970)
Battistuzzi, G., Scozzari, R., Santolamazza, P., Terrenato, L., Modiano, G.: Comparative activity of red cell adenosine deaminase allelic forms. Nature251, 25 (1974)
Brady, T.G., O'Donovan, C.J.: A study of the tissue distribution of adenosine deaminase in six mammal species. Comp. Biochem. Physiol.14, 101 (1965)
Chen, S.-H., Scott, C.R., Giblett, E.R.: Adenosine deaminase: demonstration of a “silent” gene associated with combined immunodeficiency disease. Amer. J. Hum. Gen.26, 103 (1974)
Cohen, F.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 246
Conway, E.J., Cooke, R.: The deaminases of adenosine and adenylic acid in blood and tissues. Biochem. J.33, 479 (1939)
Crosby, W.H., Munn, J.I., Furth, F.W.: Standardising a method for clinical hemoglobinometry. U.S. Armed Forces Med. J.5, 693 (1954)
Detter, J.C., Stamatoyannopoulos, G., Giblett, E.R., Motulsky, A.G.: Adenosine deaminase. Racial distribution and report of a new phenotype. J. med. Genet.7, 356 (1970)
Dissing, J., Knudsen, J.B.: A new red cell adenosine deaminase phenotype in man. Hum. Her.19, 375 (1969)
Dissing, J., Knudsen, J.B.: Human erythrocyte adenosine deaminase polymorphism in Denmark. Hum. Her.20, 178 (1970)
Dissing, J., Knudsen, J.B.: Adenosine deaminase deficiency and combined immunodeficiency syndrome. LancetII, 1316 (1972)
Edwards, Y.H., Hopkinson, D.A., Harris, H.: Adenosine deaminase isozymes in human tissues. Ann. Hum. Genet.35, 207 (1971)
Edwards, Y.H., Allen, F.H., Glenn, K.P., Lamm, L.U., Robson, E.B.: The linkage relationship of HL-A. Histocompatibility testing 1972. Eds. Dausett and Colombani. Munksgaard, Copenhagen, 1973, p. 745
Fox, J.H.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 51
Giblett, E.R., Andersen, J.E., Cohen, F., Pollara, B., Meuwissen, H.J.: Adenosine deaminase deficiency in two patients with severely impaired cellular immunity. LancetII, 1067 (1972)
Giblett, E.R., Scott, C.R., Chen, S.-H.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 109
Giblett, E.R.: Ibid., In: p. 243
Giblett, E.R., Amann, A.J., Wara, D.W., Sandmann, R., Diamond, L.K.: Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. LancetI, 1010 (1975)
Goedde, H.W., Benkmann, H.-G., Christ, I., Singh, S., Hirth, L.: Gene frequencies of red cell adenosine deaminase, adenylate kinase phosphoglucomutase, acid phosphatase and serum α-1-antitrypsin (pi)in a German population. Humangenetik10, 235 (1970)
Green, H., Chan, T.-S.: Pyrimidine starvation induced by adenosine in fibroblasts and lymphoid cells: Role of adenosine deaminase. Science182, 836 (1973)
Green, H.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 141ff.
Herzog, P., Bohatova, J.: Phenotype and gene frequencies of adenosine deaminase in Prague. Humangenetik17, 173 (1973)
Hirschhorn, R., Levytska, V., Pollara, B., Meuwissen, H.J.: Evidence for control of several different tissue-specific isozymes of adenosine deaminase by a single genetic locus. Nature New Biol.246, 200 (1973)
Hirschhorn, R.: Conversion of human erythrocyte-adenosine deaminase activity to different tissue-specific isozymes. J. Clin. Invest.55, 661 (1975)
Hirschhorn, R., Beratis, N., Rosen, F.S., Parkman, R.: Adenosine deaminase deficiency in a child diagnosed prenatally. LancetII, 73 (1975)
Hitzig, W.H.: Immunodeficiency diseases: functional classification. Boll. Ist. Sierot. Mil.53, 235 (1974)
Hopkinson, D.A., Cook, P.J.L., Harris, H.: Further data on the adenosine deaminase (ADA) polymorphism and report of a new phenotype. Ann. Hum. Gen.32, 361 (1969)
Jenkins, T.: Red blood cell adenosine deaminase deficiency in a “healthy” !Kung individual. LancetII, 736 (1973)
Jongsma, A., Van Someren, H., Westerveld, A., Hagemeijer, A., Pearson, P.: Localization of genes on human chromosomes by studies of human-chinese hamster somatic cell hybrids. Humangenetik20, 195 (1973)
Kalckar, H.M.: Differential spectrophotometry of purine compounds by means of specific enzymes. III. Studies of the enzymes of purine metabolism. J. Biol. Chem.167, 461 (1947)
Keightley, R.G., Lawton, A.R., Cooper, M.D.: Developmental defects of T and B cell lines in humans. Transplant. Rev.16, 15 (1973)
Keightley, R.G., Lawton, A.R., Cooper, M.D., Yunis, E.J.: Successful fetal liver transplantation in a child with severe combined immunodeficiency. LancetII, 850 (1975)
Klein, W.: Adenosindesaminase und ihre Verwendung zur präparativen Inosindarstellung. Hoppe-Seylersche Z.324, 163 (1961)
Lamm, L.U.: A study of red cell adenosine deaminase (ADA) types in 116 Danish families. Hum. Her.21, 63 (1971)
Meuwissen, H.J., Moore, E., Pollara, B.: Maternal marrow transplant in a patient with combined immunodeficiency disease and adenosine deaminase deficiency. Ped. Res.7, 362 (1973)
Meuwissen, H.J., Pollara, B.: Adenosine deaminase deficiency: the first inborn error of metabolism noted in immunodeficiency disease. J. Pediatr.84, 315 (1974)
Moore, E.C., Meuwissen, H.J.: Screening for ADA deficiency. J. Pediatr.85, 802 (1974)
Meuwissen, H.J., Pickering, R.J., Moore, E.C., Pollara, B.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 79
Nishihara, H., Ishikawa, S., Shinkai, K., Akedo, H.: Multiple forms of human adenosine deaminase J. Biochim. Biophys. Acta302, 429 (1973)
Nishihara, H., Ishikawa, S., Shinkai, K., Akedo, H.: Multiple forms of human adenosine deaminase II. Biochim. Biophys. Acta302, 429 (1973)
Ochs, H.D., Yount, J.E., Giblett, E.R., Chen, S.H., Scott, C.R., Wedgewood, R.J.: Adenosine deaminase deficiency and severe combined immunodeficiency syndrome. LancetI, 1393 (1973)
Parkman, R., Gelfand, E.W., Rosen, F.S., Sanderson, A., Hirschhorn, R.: Severe combined immunodeficiency and adenosine deaminase deficiency. New Engl. J. Med.292, 714 (1975)
Pollara, B., Meuwissen, H.J.: Combined immunodeficiency disease and ADA deficiency. LancetII, 1324 (1973)
Pollara, B., Pickering, R.J., Meuwissen, H.J.: Combined immunodeficiency disease and adenosine deaminase deficiency, an inborn error of metabolism. Ped. Res.7, 362 (1973)
Pollara, B., Moore, J.J., Pickering, M.S.R., Gabrielsen, A.E., Meuwissen, H.J.: Combined immunodeficiency disease: An inborn error of purine metabolism. Birth Defects11, 120 (1975)
Polmar, S.H., Wetzler, E.M., Stern, R.G., Hirschorn, R.: Restoration of in-vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency. LancetII, 743 (1975)
Radam, G., Strauch, H.: Zur Differenzierung der Varianten 5-1 und 6-1 im Adenosindesaminase-Polymorphismus, Nachweis des neuen Phänotyps ADA 5-2 in der CSSR. Humangenetik26, 151 (1975)
Renninger, W., Bimbose, Ch.: Zur Genetik der Erythrozyten Adenosindesaminase (ADA) Genfrequenzen und Familienuntersuchungen. Humangenetik9, 34 (1970)
Ritter, H., Wendt, G.G., Tariverdian, G., Zilch, J., Rube, M., Kirchberg, G.: Genetics and linkage analysis of adenosine deaminase. Humangenetik14, 69 (1971)
Ruddle, F.H.: Linkage analysis in man by somatic cell genetics. Nature242, 165 (1973)
Shinoda, T.: Polymorphism of red cell adenosine deaminase in the Japanese population. Jap. J. Genet.45, 147 (1970)
Sonneborn, H.-H., Renninger, W.: Genfrequenzuntersuchungen der Adenosindesaminase-Isoenzyme mit einer neuen Technik. Humangenetik10, 188 (1970)
Sonneborn, H.-H.: Gleichzeitige Auftrennung von AK- und ADA-Isoenzymen auf einer Folie. Humangenetik15, 87 (1972)
Sonneborn, H.-H.: Comments on the determination of isoenzyme polymorphism (ADA, AK, 6-PGD, PGM) by cellulose acetate electrophoresis. Humangenetik17, 49 (1972)
Sørensen, S.A.: The polymorphism of red cell acid phosphatase, phosphoglucomutase, adenosine deaminase and adenylate kinase in twins. Hum. Her.24, 236 (1974)
Spencer, N., Hopkinson, D.A., Harris, H.: Adenosine deaminase polymorphism in man. Ann. Hum. Gen.32, 9 (1968)
Szeinberg, A., Pipano, S., Rozansky, T., Ravia, N.: Frequency of red cell adenosine deaminase phenotypes in several population groups in Israel. Hum. Her.21, 357 (1971)
Tariwerdian, G., Ritter, H.: Adenosine deaminase polymorphism (EC: 3.5.4.4.) formal genetics and linkage relations. Humangenetik7, 176 (1969)
Tischfield, J.A., Creagan, R.P., Nichols, E.A., Ruddle, F.H.: Assignment of a gene for adenosine deaminase to human chromosome 20. Hum. Her.24, 1 (1974)
Van Belle, H.: Uptake and deamination of adenosine by blood species differences, effect of pH ions, temperature, and metabolic inhibitors. Biochim. Biophys. Acta192, 124 (1969)
Welch, Q.B., Lie-Injo, I.E., Garresan, J.: Erythrocyte adenosine deaminase in Malaysians. Hum. Her.25, 69 (1975)
Wara, D.W., Ammann, A.J.: In: Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect. Academic Press, Inc. New York, San Francisco, London (1974), p. 251
Wolfson, J.J., Cross, V.F.: Ibid., In: p. 262
Wüst, H.: Further studies on the adenosine deaminase ADA-polymorphism in Austria. Vox Sang.21, 443 (1971)
Wüst, H.: Adenosine deaminase in lymphocytes and its electrophoretic separation. Hum. Her.21, 607 (1971)
Yount, J., Nichols, P., Ochs, H., Hammar, S.P., Scott, C.R., Chen, S.-H., Giblett, E.R., Wedgwood, R.J.: Absence of erythrocyte adenosine deaminase associated with severe combined immunodeficiency. J. Pediatr.84, 173 (1974)
Author information
Authors and Affiliations
Additional information
Mit Unterstützung der Deutschen Forschungsgemeinschaft (Be 496/3)
Rights and permissions
About this article
Cite this article
Belohradsky, B.H., Hennig, N., Marget, W. et al. Adenosindesaminase-Mangel bei primären Immundefizienzen. Klin Wochenschr 54, 1109–1115 (1976). https://doi.org/10.1007/BF01469254
Issue Date:
DOI: https://doi.org/10.1007/BF01469254