Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct 8;6(4):77.
doi: 10.3390/ijns6040077.

Considering Proximal Urea Cycle Disorders in Expanded Newborn Screening

Tania Vasquez-Loarte  1 , John D Thompson  2 , J Lawrence Merritt 2nd  3
Affiliations
Review

Considering Proximal Urea Cycle Disorders in Expanded Newborn Screening

Tania Vasquez-Loarte et al. Int J Neonatal Screen. .

Abstract

Proximal urea cycle disorders (PUCDs) have adverse outcomes such as intellectual disability and death, which may benefit from newborn screening (NBS) through early detection and prevention with early treatment. Ornithine transcarbamylase deficiency (OTCD) and carbamoyl phosphate synthetase 1 deficiency (CPS1D) are screened in six and eight states in the United States. We analyzed current evidence to see if it supports inclusion of PUCDs in the NBS panels based upon prevention potential, medical, diagnostic, treatment, and public health rationales. A literature review was performed in PubMed using MESH terms for OTCD, CPS1D, and NAGSD. A systematic review was performed in the hallmark of NBS inclusion criteria. We reviewed 31 articles. Molecular and biochemical diagnosis is available to provide diagnostic evidence. Untreated PUCDs have a significant burden with considerable developmental delay and mortality that may improve with early treatment. Tandem mass spectrometry can be used for NBS for PUCDs; however, citrulline and glutamine alone are not specific. Medical treatments currently available for PUCDs meet existing medical, diagnostic, treatment, and public health rationales. Improvement in NBS algorithms to increase sensitivity and specificity will allow earlier diagnosis and treatment to potentially improve disability and mortality rates.

Keywords: N-acetyl glutamate synthetase deficiency; NBS; carbamoyl phosphate synthetase 1 deficiency; neonatal screening; newborn screening; ornithine transcarbamylase deficiency; proximal urea cycle disorders; public health.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Newborn screening for Urea Cycle Disorders in the United States, 2020.
See this image and copyright information in PMC

References

    1. Health Resources & Services Administration Recommended Uniform Screening Panel. [(accessed on 5 December 2019)]; Available online: https://www.hrsa.gov/advisory-committees/heritable-disorders/rusp/index.....
    1. Washington State Board of Health Washington State Board of Health Process to Evaluate Conditions for Inclusion in the Required Newborn Screening Panel. [(accessed on 17 September 2019)]; Available online: https://sboh.wa.gov/Portals/7/Doc/HealthyBehaviors/NBS/NewbornScreeningC....
    1. Nucup-Villaruz C S.S. The Compelling Benefits of Routine 2nd NBS: A Fifteen-Year Review in Washington State. [(accessed on 18 September 2019)]; Available online: https://www.aphl.org/conferences/proceedings/Documents/2014/NBS/37Nucup-....
    1. Washington State Board of Health Healthcare Provider Manual: The Complete Guide to Newborn Screening in Washington State. [(accessed on 18 September 2019)]; Available online: https://www.doh.wa.gov/Portals/1/Documents/5220/ProviderManual.pdf.
    1. Burgard P., Kölker S., Haege G., Lindner M., Hoffmann G.F. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders—Review and meta-analysis of observational studies published over more than 35 years. J. Inherit. Metab. Dis. 2016;39:219–229. doi: 10.1007/s10545-015-9901-1. - DOI - PubMed