DOI: 10.1126/science.155.3770.1682. Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis

Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis

10.1126/science.155.3770.1682

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

A sex-linked familial neurological disease consisting of cerebral palsy, mental retardation, choreoathetosis, and compulsive aggressive behavior is associated with a loss of an enzyme that participates in purine metabolism, namely, hypoxanthine-guanine phosphoribosyltransferase. The production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis. This is the first example of a relation between a specific enzyme defect and abnormal compulsive behavior. It is also the first enzyme defect in purine metabolism demonstrated in a neurological disease.

Bibliography

Seegmiller, J. E., Rosenbloom, F. M., & Kelley, W. N. (1967). Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis. Science, 155(3770), 1682â1684.

Authors 3

J. Edwin Seegmiller (first)
Frederick M. Rosenbloom (additional)
William N. Kelley (additional)

References 19 Referenced 932

BENNETT, L.L., STUDIES ON THE MODE OF ACTION OF AZASERINE, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 64: 423 (1956). (10.1016/0003-9861(56)90286-7) / ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (1956)
BROCKMAN, R.W., BIOCHEMICAL ASPECTS OF MERCAPTOPURINE INHIBITION AND RESISTANCE, CANCER RESEARCH 23: 1191 (1963). / CANCER RESEARCH (1963)
BROCKMAN, R.W., RESISTANCE TO PURINE ANTAGONISTS IN EXPERIMENTAL LEUKEMIA SYSTEMS, CANCER RESEARCH 25: 1596 (1965). / CANCER RESEARCH (1965)
DAVIDSON, J.D., PURINE NUCLEOTIDE PYROPHOSPHORYLASES IN 6-MERCAPTOPURINE-SENSITIVE + -RESISTANT HUMAN LEUKEMIAS, CANCER RESEARCH 24: 261 (1964). / CANCER RESEARCH (1964)
DAVIDSON, R.G., DEMONSTRATION OF 2 POPULATIONS OF CELLS IN HUMAN FEMALE HETEROZYGOUS FOR GLUCOSE-6-PHOSPHATEDEHYDROGENASE VARIANTS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 50: 481 (1963). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1963)
HENDERSON, J.F., FEEDBACK INHIBITION OF PURINE BIOSYNTHESIS IN ASCITES TUMOR CELLS, JOURNAL OF BIOLOGICAL CHEMISTRY 237: 2631 (1962). (10.1016/S0021-9258(19)73799-5) / JOURNAL OF BIOLOGICAL CHEMISTRY (1962)
HOEFNAGEL, D, THE SYNDROME OF ATHETOID CEREBRAL-PALSY, MENTAL DEFICIENCY, SELF-MUTILATION AND HYPERURICEMIA, JOURNAL OF MENTAL DEFICIENCY RESEARCH 9: 69 (1965). / JOURNAL OF MENTAL DEFICIENCY RESEARCH (1965)
HOEFNAGEL, D, HEREDITARY CHOREOATHETOSIS SELF-MUTILATION AND HYPERURICEMIA IN YOUNG MALES, NEW ENGLAND JOURNAL OF MEDICINE 273: 130 (1965). (10.1056/NEJM196507152730303) / NEW ENGLAND JOURNAL OF MEDICINE (1965)
LEPAGE, G.A., PURINETHIOLS AS FEEDBACK INHIBITORS OF PURINE SYNTHESIS IN ASCITES TUMOR CELLS, CANCER RESEARCH 21: 642 (1961). / CANCER RESEARCH (1961)
10.1016/0002-9343(64)90104-4
LEVENBERG, B, BIOSYNTHESIS OF THE PURINES .15. THE EFFECT OF AZA-L-SERINE AND 6-DIAZO-5-OXO-L-NORLEUCINE ON INOSINIC ACID BIOSYNTHESIS DE NOVO, JOURNAL OF BIOLOGICAL CHEMISTRY 225: 163 (1957). (10.1016/S0021-9258(18)64919-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1957)
NYHAN, W.L., A FAMILIAL DISORDER OF URIC ACID METABOLISM AND CENTRAL NERVOUS SYSTEM FUNCTION .2., JOURNAL OF PEDIATRICS 67: 257 (1965). (10.1016/S0022-3476(65)80249-9) / JOURNAL OF PEDIATRICS (1965)
REED, W.B., HYPERURICEMIA WITH SELF-MUTILATION AND CHOREO-ATHETOSIS, ARCHIVES OF DERMATOLOGY 94: 194 (1966). (10.1001/archderm.1966.01600260086011) / ARCHIVES OF DERMATOLOGY (1966)
SASS, J.K., JUVENILE GOUT WITH BRAIN INVOLVEMENT, ARCHIVES OF NEUROLOGY 13: 639 (1965). (10.1001/archneur.1965.00470060075008) / ARCHIVES OF NEUROLOGY (1965)
SEEGMILLER, J.E., URIC ACID PRODUCTION IN GOUT, JOURNAL OF CLINICAL INVESTIGATION 40: 1304 (1961). (10.1172/JCI104360) / JOURNAL OF CLINICAL INVESTIGATION (1961)
SHAPIRO, S.L., X-LINKED RECESSIVE INHERITANCE OF A SYNDROME OF MENTAL RETARDATION WITH HYPERURICEMIA, PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE 122: 609 (1966). (10.3181/00379727-122-31204) / PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE (1966)
SMITH M.G. IN PREPARATION.
Sorensen, L. B., Nature 213: 1122 (1967). / Nature (1967)
SORENSEN, L.B., SUPPRESSION OF SHUNT PATHWAY IN PRIMARY GOUT BY AZATHIOPRINE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 55: 571 (1966). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1966)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 7:08 a.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 4:58 a.m.)
Indexed	1 week, 1 day ago (Aug. 19, 2025, 6:18 a.m.)
Issued	58 years, 4 months ago (March 31, 1967)
Published	58 years, 4 months ago (March 31, 1967)
Published Print	58 years, 4 months ago (March 31, 1967)

Funders 0

None

BibTeX

@article{Seegmiller_1967, title={Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis}, volume={155}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.155.3770.1682}, DOI={10.1126/science.155.3770.1682}, number={3770}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Seegmiller, J. Edwin and Rosenbloom, Frederick M. and Kelley, William N.}, year={1967}, month=mar, pages={1682–1684} }

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