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Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia

Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for argina...

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Autores principales: Huang, Yue, Sharma, Rajesh, Feigenbaum, Annette, Lee, Chung, Sahai, Inderneel, Sanchez Russo, Rossana, Neira, Juanita, Brooks, Susan Sklower, Jackson, Kelly E., Wong, Derek, Cederbaum, Stephen, Lacbawan, Felicitas L., Rowland, Charles M., Tanpaiboon, Pranoot, Salazar, Denise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937551/
https://www.ncbi.nlm.nih.gov/pubmed/33732618
http://dx.doi.org/10.1016/j.ymgmr.2021.100735
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author Huang, Yue
Sharma, Rajesh
Feigenbaum, Annette
Lee, Chung
Sahai, Inderneel
Sanchez Russo, Rossana
Neira, Juanita
Brooks, Susan Sklower
Jackson, Kelly E.
Wong, Derek
Cederbaum, Stephen
Lacbawan, Felicitas L.
Rowland, Charles M.
Tanpaiboon, Pranoot
Salazar, Denise
author_facet Huang, Yue
Sharma, Rajesh
Feigenbaum, Annette
Lee, Chung
Sahai, Inderneel
Sanchez Russo, Rossana
Neira, Juanita
Brooks, Susan Sklower
Jackson, Kelly E.
Wong, Derek
Cederbaum, Stephen
Lacbawan, Felicitas L.
Rowland, Charles M.
Tanpaiboon, Pranoot
Salazar, Denise
author_sort Huang, Yue
collection PubMed
description Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Here, we report 14 arginase deficiency cases, including two patients with positive NBS for hyperargininemia in whom the diagnosis of arginase deficiency was delayed owing to normal or near normal plasma arginine levels on follow-up testing. To improve the detection capability for arginase deficiency, we evaluated plasma Arg/Orn ratio as a secondary diagnostic marker in positive NBS cases for hyperargininemia. We found that plasma Arg/Orn ratio combined with plasma arginine was a better marker than plasma arginine alone to differentiate patients with arginase deficiency from unaffected newborns. In fact, elevated plasma arginine in combination with an Arg/Orn ratio of ≥1.4 identified all 14 arginase deficiency cases. In addition, we examined the impact of age on plasma arginine and ornithine levels. Plasma arginine increased 0.94 μmol/L/day while ornithine was essentially unchanged in the first 31 days of life, which resulted in a similar increasing trend for the Arg/Orn ratio (0.01/day). This study demonstrated that plasma Arg/Orn ratio as a secondary diagnostic marker improved the detection capability for arginase deficiency in newborns with hyperargininemia, which will allow timely detection of arginase deficiency and hence initiation of treatment before developing symptoms.
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spelling pubmed-79375512021-03-16 Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia Huang, Yue Sharma, Rajesh Feigenbaum, Annette Lee, Chung Sahai, Inderneel Sanchez Russo, Rossana Neira, Juanita Brooks, Susan Sklower Jackson, Kelly E. Wong, Derek Cederbaum, Stephen Lacbawan, Felicitas L. Rowland, Charles M. Tanpaiboon, Pranoot Salazar, Denise Mol Genet Metab Rep Research Paper Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Here, we report 14 arginase deficiency cases, including two patients with positive NBS for hyperargininemia in whom the diagnosis of arginase deficiency was delayed owing to normal or near normal plasma arginine levels on follow-up testing. To improve the detection capability for arginase deficiency, we evaluated plasma Arg/Orn ratio as a secondary diagnostic marker in positive NBS cases for hyperargininemia. We found that plasma Arg/Orn ratio combined with plasma arginine was a better marker than plasma arginine alone to differentiate patients with arginase deficiency from unaffected newborns. In fact, elevated plasma arginine in combination with an Arg/Orn ratio of ≥1.4 identified all 14 arginase deficiency cases. In addition, we examined the impact of age on plasma arginine and ornithine levels. Plasma arginine increased 0.94 μmol/L/day while ornithine was essentially unchanged in the first 31 days of life, which resulted in a similar increasing trend for the Arg/Orn ratio (0.01/day). This study demonstrated that plasma Arg/Orn ratio as a secondary diagnostic marker improved the detection capability for arginase deficiency in newborns with hyperargininemia, which will allow timely detection of arginase deficiency and hence initiation of treatment before developing symptoms. Elsevier 2021-03-03 /pmc/articles/PMC7937551/ /pubmed/33732618 http://dx.doi.org/10.1016/j.ymgmr.2021.100735 Text en © 2021 Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Huang, Yue
Sharma, Rajesh
Feigenbaum, Annette
Lee, Chung
Sahai, Inderneel
Sanchez Russo, Rossana
Neira, Juanita
Brooks, Susan Sklower
Jackson, Kelly E.
Wong, Derek
Cederbaum, Stephen
Lacbawan, Felicitas L.
Rowland, Charles M.
Tanpaiboon, Pranoot
Salazar, Denise
Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title_full Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title_fullStr Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title_full_unstemmed Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title_short Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
title_sort arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937551/
https://www.ncbi.nlm.nih.gov/pubmed/33732618
http://dx.doi.org/10.1016/j.ymgmr.2021.100735
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