NDLI: The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dimmock, David P. Trapane, Pamela Feigenbaum, Annette Keegan, Catherine E. Cederbaum, Stephen Gibson, James Gambello, Michael J. Vaux, Keith Ward, Patricia Rice, Gregory M. Wolff, Jon A. O'Brien, William E. Fang, Ping
Description	Country affiliation: United States Author Affiliation: Dimmock DP ( Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. ddimmock@hmgc.mcw.edu)
Abstract	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.
File Format	HTM / HTML
ISSN	15524825
e-ISSN	15524833
DOI	10.1002/ajmg.a.32527
Journal	American Journal of Medical Genetics Part A
Issue Number	22
Volume Number	146A
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2008-11-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Genetics Argininosuccinate Synthase Blood Genetics Citrullinemia Enzymology Adolescent Child, Preschool Citrulline Diagnosis Therapy Dna Mutational Analysis Infant Infant, Newborn Neonatal Screening Pregnancy Pregnancy Complications Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article Case study
Subject	Genetics Genetics (clinical)

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