Document Detail


Differences in purine metabolism in patients with Down's syndrome.
MedLine Citation:
PMID:  8123996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three enzymes intervening in de novo purine synthesis, as well as cystathionine B-synthetase, have been mapped to chromosome 21. In order to gain a better understanding of purine synthesis anomalies in Down's syndrome, the present authors studied the variations in mitotic index of lymphocyte cultures to which various inhibitors or metabolites of purine synthesis had been added. In spite of common gene dosage effects, unexpected and highly significant differences were noted between Down's syndrome patients without complications and those presenting with additional psychotic features. In Down's syndrome patients without complications, a highly significant decrease in mitotic index was noted in the presence of exogenous inosine. A significant decrease in the presence of adenosine and guanosine was also noted. These findings are in keeping with the expected metabolic repercussions of genes mapped to chromosome 21. In Down's syndrome patients with psychotic complications, the in vitro reactions were quite different. A paradoxal increase in mitotic index was noted in the presence of inosine and of adenosine, but the response to guanosine did not differ from that observed in normal controls. These findings were unexpected and seem to indicate that, in spite of the gene dosage effect, psychotic Down's syndrome patients are unable to compensate abnormal purine synthesis and resulting imbalances. Furthermore, a marked difference in purine metabolic reactions was noted between Down's syndrome patients receiving supplemental folic/folinic acid and those on no therapy. This suggests that some modulation of the gene dosage effect may be possible.
Authors:
M A Peeters; A Megarbane; F Cattaneo; M O Rethore; J Lejeune
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of intellectual disability research : JIDR     Volume:  37 ( Pt 6)     ISSN:  0964-2633     ISO Abbreviation:  J Intellect Disabil Res     Publication Date:  1993 Dec 
Date Detail:
Created Date:  1994-04-14     Completed Date:  1994-04-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9206090     Medline TA:  J Intellect Disabil Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  491-505     Citation Subset:  IM    
Affiliation:
Institut de Progenèse, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / deficiency,  pharmacology
Adolescent
Child
Chromosomes, Human, Pair 21
Down Syndrome / genetics,  metabolism*,  psychology
Female
Folic Acid / administration & dosage,  pharmacology
Guanosine / deficiency,  pharmacology
Humans
Inosine / pharmacology
Male
Mitotic Index / drug effects
Phenotype
Purines / metabolism*
Chemical
Reg. No./Substance:
0/Purines; 118-00-3/Guanosine; 58-61-7/Adenosine; 58-63-9/Inosine; 59-30-3/Folic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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