Linked Life Data

15517380

Source:http://linkedlifedata.com/resource/pubmed/id/15517380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-7
pubmed:abstractText
Delta1-pyrroline-5-carboxylate synthase (P5CS) catalyses the reduction of glutamate to Delta1-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. Recently, we reported a newly recognised inborn error due to deficiency of P5CS in two sibs, one presenting at birth with hypotonia, dysmorphic signs, pes planus and clonic seizures. Both developed progressive neurodegeneration and peripheral neuropathy, joint laxity, skin hyperelasticity and bilateral subcapsular cataracts. Their metabolic phenotype includes mild hyperammonaemia, hypo-ornithinaemia, hypocitrullinaemia, hypo-argininaemia and hypoprolinaemia. Incorporation of 3H-proline into protein was deficient in fibroblasts incubated with 3H-glutamate. Both patients are homozygous for the missense mutation R84Q in P5CS. Here, we describe the clinical phenotype of the sibs in detail and show that a relative deficiency of urea cycle intermediates (ornithine, citrulline and arginine) during fasting periods results in a paradoxical hyperammonaemia. Furthermore, we show the results of ornithine loading tests and indirect enzyme studies corroborating the biological significance of the defect in P5CS in vivo. CONCLUSION: The metabolic phenotype of Delta1-pyrroline-5-carboxylate synthase deficiency is easily missed. The combination of low levels of ornithine, citrulline, arginine and proline plus a tendency to hyperammonaemia or one of the above together with a clinical phenotype of neurodegeneration with peripheral neuropathy and/or cataracts and connective tissue manifestations should suggest this disorder. Early recognition would allow a therapeutic trial with citrulline and proline.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0340-6199
pubmed:author
pubmed:issnType
Print
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Delta1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline.
pubmed:affiliation
Division of Metabolism and Molecular Paediatrics, University Children's Hospital, Zurich, Switzerland.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't