Document Detail

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia.
MedLine Citation:
PMID:  18925679     Owner:  NLM     Status:  MEDLINE    
Expanded newborn screening detects patients with modest elevations in citrulline; however it is currently unclear how to treat these patients and how to counsel their parents. In order to begin to address these issues, we compared the clinical, biochemical, and molecular features of 10 patients with mildly elevated citrulline levels. Three patients presented with clinical illness whereas seven came to attention as a result of expanded newborn screening. One patient presented during pregnancy and responded promptly to IV sodium phenylacetate/sodium benzoate and arginine therapy with no long-term adverse effects on mother or fetus. Two children presented with neurocognitive dysfunction, one of these responded dramatically to dietary protein reduction. ASS enzyme activity was not deficient in all patients with biallelic mutations suggesting this test cannot exclude the ASS1 locus in patients with mildly elevated plasma citrulline. Conversely, all symptomatic patients who were tested had deficient activity. We describe four unreported mutations (p.Y291S, p.R272H, p.F72L, and p.L88I), as well as the common p.W179R mutation. In silico algorithms were inconsistent in predicting the pathogenicity of mutations. The cognitive benefit in one patient of protein restriction and the lack of adverse outcome in seven others restricted from birth, suggest a role for protein restriction and continued monitoring to prevent neurocognitive dysfunction.
David P Dimmock; Pamela Trapane; Annette Feigenbaum; Catherine E Keegan; Stephen Cederbaum; James Gibson; Michael J Gambello; Keith Vaux; Patricia Ward; Gregory M Rice; Jon A Wolff; William E O'Brien; Ping Fang
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of medical genetics. Part A     Volume:  146A     ISSN:  1552-4833     ISO Abbreviation:  Am. J. Med. Genet. A     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-12-10     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  101235741     Medline TA:  Am J Med Genet A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2885-90     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
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MeSH Terms
Argininosuccinate Synthase / blood*,  genetics*
Child, Preschool
Citrulline / blood
Citrullinemia / diagnosis,  enzymology*,  genetics*,  therapy
DNA Mutational Analysis
Infant, Newborn
Neonatal Screening
Pregnancy Complications / enzymology,  genetics,  therapy
Grant Support
K12 RR017665-05/RR/NCRR NIH HHS; K12 RR17665/RR/NCRR NIH HHS
Reg. No./Substance:
372-75-8/Citrulline; EC Synthase
Erratum In:
Am J Med Genet A. 2010 Apr;152A(4):1061

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

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