Activity of the liver enzyme ornithine carbamoyltransferase (OTC) in blood: LC-MS/MS assay for non-invasive diagnosis of ornithine carbamoyltransferase deficiency
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10364224" target="_blank" >RIV/00216208:11110/17:10364224 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/17:10364224
Result on the web
<a href="http://dx.doi.org/10.1515/cclm-2016-0715" target="_blank" >http://dx.doi.org/10.1515/cclm-2016-0715</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1515/cclm-2016-0715" target="_blank" >10.1515/cclm-2016-0715</a>
Alternative languages
Result language
angličtina
Original language name
Activity of the liver enzyme ornithine carbamoyltransferase (OTC) in blood: LC-MS/MS assay for non-invasive diagnosis of ornithine carbamoyltransferase deficiency
Original language description
Background: Liver enzymes are released from hepatocytes into circulation and their activity can be measured in the blood. We examined whether the plasma activity of the liver enzyme ornithine carbamoyltransferase, determined by a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay, could be utilized for the detection of OTC deficiency (OTCD), an X-linked inborn error of the urea cycle. Methods: The plasma ornithine carbamoyltransferase (OTC) activity was assayed in the reverse reaction using isotopically labeled citrulline-d4 as a substrate and by determination of the product, ornithine-d4, by LC-MS/MS analysis. Results: The plasma OTC activity in the controls was in the range of 111-658 pkat/L (n = 49, median 272 pkat/L), and the activity increased linearly with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in patients with hepatopathy. The OTC activity was subsequently determined in 32 individuals carrying mutations in the OTC gene, and OTC/ALT and OTC/AST ratios were calculated to account for the degree of hepatopathy, which is a common finding in OTCD. The OTC/ALT ratio enabled clear differentiation of OTCD hemizygotes (n = 11, range 0-69 x 10(-6)) from controls (504-3440 x 10(-6)). This ratio also enabled the detection of 11 of 12 symptomatic heterozygotes (range 38-794 x 10(-6)), while this marker did not allow for reliable differentiation of asymptomatic heterozygotes (n = 9) from controls. Conclusions: LC-MS/MS assay of plasma OTC activity enabled the detection of all hemizygous and the majority of symptomatic heterozygous OTCD patients in the tested cohort. This study demonstrates that non-invasive assay of enzymes expressed predominantly in the liver could be used as an alternative approach for diagnosing inborn errors of metabolism.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30209 - Paediatrics
Result continuities
Project
<a href="/en/project/NT14159" target="_blank" >NT14159: Plasma activities of intracellular enzymes in selected inborn errors of metabolism - suitability for diagnosis and for predicting responsiveness to therapy.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Chemistry and Laboratory Medicine
ISSN
1434-6621
e-ISSN
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Volume of the periodical
55
Issue of the periodical within the volume
8
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
1168-1177
UT code for WoS article
000405506000022
EID of the result in the Scopus database
2-s2.0-85025107396