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Arch Dis Child. 1980 June; 55(6): 452–457.
PMCID: PMC1626931

Severe combined immunodeficiency and adenosine deaminase deficiency: failure of enzyme replacement therapy.


A first-born baby boy presented at age 3 months with persistent diarrhoea, failure to thrive, and recurrent bacterial and fungal infections. Severe combined immunodeficiency was demonstrated. A deficiency of adenosine deaminase (ADA) activity was suggested by the presence of extensive skeletal abnormalities, and the ADA activity in erythrocyte and leucocyte lysates was < 0.005 nmol/h per mg protein. Culture of ADA-negative peripheral blood mononuclear cells, together with purified calf ADA, did not alter the absent phytohaemagglutinin response. Treatment with immunoglobulin, pentamidine, and co-trimoxazole was started and a programme of ADA enzyme replacement, with infusions of plasma and frozen irradiated erythrocytes, was begun at age 4 months and achieved blood ADA levels in excess of 30 nmol/h per mg haemoglobin. Although resolution of the interstitial pneumonitis and skeletal abnormalities was observed, there was no evidence of immunological reconstitution. The patient died at age 17 months after a parainfluenza pneumonitis. Features of importance in predicting lack of benefit from enzyme replacement by erythrocyte infusion in ADA-negative severe combined immunodeficiency appear to be early clinical presentation with associated severe skeletal abnormalities, a very low level of residual ADA activity in peripheral blood mononuclear cells, and lack of effect of exogenous ADA on the absent in vitro mitogen response of ADA-negative blood mononuclear cells.

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Selected References

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  • Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. [PubMed]
  • Meuwissen HJ, Pollara B, Pickering RJ. Combined immunodeficiency disease associated with adenosine deaminase deficiency. Report on a workshop held in Albany, New York, October 1, 1973. J Pediatr. 1975 Feb;86(2):169–181. [PubMed]
  • Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med. 1976 Dec 9;295(24):1337–1343. [PubMed]
  • Schmalstieg FC, Mills GC, Nelson JA, May LT, Goldman AS, Goldblum RM. Limited effect of erythrocyte and plasma infusions in adenosine deaminase deficiency. J Pediatr. 1978 Oct;93(4):597–603. [PubMed]
  • Coleman MS, Donofrio J, Hutton JJ, Hahn L, Daoud A, Lampkin B, Dyminski J. Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency. J Biol Chem. 1978 Mar 10;253(5):1619–1626. [PubMed]
  • Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. [PubMed]
  • Böyum A. A one-stage procedure for isolation of granulocytes and lymphocytes from human blood. General sedimentation properties of white blood cells in a 1g gravity field. Scand J Clin Lab Invest Suppl. 1968;97:51–76. [PubMed]
  • Cooper DA, Petts V, Luckhurst E, Biggs JC, Penny R. T and B cell populations in blood and lymph node in lymphoproliferative disease. Br J Cancer. 1975 May;31(5):550–558. [PubMed]
  • Ziegler JB, Hansen P, Penny R. Intrinsic lymphocyte defect in Hodgkin's disease: analysis of the phytohemagglutinin dose-response. Clin Immunol Immunopathol. 1975 Mar;3(4):451–460. [PubMed]
  • Jondal M, Holm G, Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. [PMC free article] [PubMed]
  • Bianco C, Patrick R, Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. [PMC free article] [PubMed]
  • Papamichail M, Brown JC, Holborow EJ. Immunoglobulins on the surface of human lymphocytes. Lancet. 1971 Oct 16;2(7729):850–852. [PubMed]
  • van der Weyden MB, Bailey L. A micromethod for determining adenosine deaminase and purine nucleoside phosphorylase activity in cells from human peripheral blood. Clin Chim Acta. 1978 Jan 2;82(1-2):179–184. [PubMed]
  • Lee CH, Evans SP, Rozenberg MC, Bagnara AS, Ziegler JB, Van der Weyden MB. In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency. Blood. 1979 Mar;53(3):465–471. [PubMed]
  • Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW., Jr Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1978 Jan;75(1):472–476. [PubMed]
  • Uberti J, Lightbody JJ, Wolf JW, Anderson JA, Reid RH, Johnson RM. The effect of adenosine on mitogenesis of ADA-deficient lymphocytes. Clin Immunol Immunopathol. 1978 Aug;10(4):446–458. [PubMed]
  • Donofrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J. Overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease. J Clin Invest. 1978 Oct;62(4):884–887. [PMC free article] [PubMed]
  • Polmar SH, Wetzler EM, Stern RC, Hirschhorn R. Restoration of in-vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency. Lancet. 1975 Oct 18;2(7938):743–746. [PubMed]

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