Abstract
The deoxynucleotide, dATP, is elevated 50- to 1,000-fold above normal in erythrocytes, lymphocytes, and bone marrow from a child with adenosine deaminase deficiency and severe combined immunodeficiency disease. The child, when 17 mo of age, was also excreting approximately 30 mg of deoxyadenosine per day in urine (normal is less than 0.1 mg/day). Urinary excretion of uric acid was decreased. Elevated dATP levels in lymphocytes and bone marrow, and increased urinary excretion of deoxyadenosine, persisted despite hypertransfusion of the child with irradiated erythrocytes from a donor with normal adenosine deaminase. Overproduction of deoxynucleotides by increased salvage of adenosine appears to be the primary metabolic abnormality in patients with adenosine de aminase deficiency.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- APOSHIAN H. V., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. IX. The polymerase formed after T2 bacteriophage infection of Escherichia coli: a new enzyme. J Biol Chem. 1962 Feb;237:519–525. [PubMed] [Google Scholar]
- Cohen A., Hirschhorn R., Horowitz S. D., Rubinstein A., Polmar S. H., Hong R., Martin D. W., 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. doi: 10.1073/pnas.75.1.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coleman M. S., Donofrio J., Hutton J. J., 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] [Google Scholar]
- Coleman M. S., Hutton J. J., Bollum F. J. DNA polymerases in normal and leukemic human hematopoietic cells. Blood. 1974 Jul;44(1):19–32. [PubMed] [Google Scholar]
- Duch D. S., Laskowski M., Sr A sensitive method for the determination of RNA in DNA and vice versa. Anal Biochem. 1971 Nov;44(1):42–48. doi: 10.1016/0003-2697(71)90343-5. [DOI] [PubMed] [Google Scholar]
- Follmann H. Enzymatic reduction of ribonucleotides: biosynthesis pathway of deoxyribonucleotides. Angew Chem Int Ed Engl. 1974 Sep;13(9):569–579. doi: 10.1002/anie.197405691. [DOI] [PubMed] [Google Scholar]
- Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
- Polmar S. H., Stern R. C., Schwartz A. L., Wetzler E. M., Chase P. A., Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med. 1976 Dec 9;295(24):1337–1343. doi: 10.1056/NEJM197612092952402. [DOI] [PubMed] [Google Scholar]
- Solter A. W., Handschumacher R. E. A rapid quantitative determination of deoxyribonucleoside triphosphates based on the enzymatic synthesis of DNA. Biochim Biophys Acta. 1969 Feb 18;174(2):585–590. doi: 10.1016/0005-2787(69)90288-3. [DOI] [PubMed] [Google Scholar]