Document Detail


Outcome of pregnancy in the rat with mild hyperphenylalaninaemia and hypertyrosinaemia: implications for the management of "human maternal PKU".
MedLine Citation:
PMID:  3939586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In attempting to determine the effects of mildly elevated maternal phenylalanine (Phe) blood levels on the developing fetal rat brain, a dietary supplement of Phe was given, under taste cover of Aspartame. Phe and tyrosine (Tyr) levels were mildly elevated throughout pregnancy without evidence of malnutrition. Mild hyperphenylalaninaemia with concurrent hypertyrosinaemia induced in rats prior to conception resulted in microcephaly and lasting behavioural problems in the offspring, specifically hyperactivity and learning difficulties. Dams fed Tyr to produce Tyr levels equivalent to the Phe-fed animals showed only the learning difficulties among the offspring. alpha-Methyl Phe, a Phe hydroxylase inhibitor, fed in conjunction with Phe, at the level relevant to these experiments, resulted in raised Tyr levels and does not provide a better method of determining whether mildly elevated maternal Phe levels alone, or Phe and Tyr in combination, cause the abnormality found in the offspring of Phe-supplemented dams. Therapeutic addition of Tyr to diets of mothers with even mild hyperphenylalaninaemia should be approached with caution as mild co-elevation of Phe and Tyr in the fetus may be harmful. In the face of such a possible therapeutic dilemma alternatives, such as dietary additions of other essential amino acids to limit fetal brain damage, need to be explored.
Authors:
S A Lewis; I C Lyon; R B Elliott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  8     ISSN:  0141-8955     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  1985  
Date Detail:
Created Date:  1987-03-04     Completed Date:  1987-03-04     Revised Date:  2007-03-21    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  113-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Diseases / etiology*
Discrimination (Psychology)
Disease Models, Animal*
Female
Motor Activity
Phenylalanine / blood
Phenylketonurias* / therapy
Pregnancy
Pregnancy Complications* / therapy
Prenatal Exposure Delayed Effects*
Rats
Space Perception
Tyrosine / blood
Chemical
Reg. No./Substance:
55520-40-6/Tyrosine; 63-91-2/Phenylalanine

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


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