Case Report of Argininemia: The Utility of the Arginine/Ornithine Ratio for Newborn Screening (NBS)

Jay, Allison; Seeterlin, Mary; Stanley, Eleanor; Grier, Robert E.

doi:10.1007/8904_2012_190

Cited by 13 publications

(11 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expanded NBS for amino acid disorders using tandem mass spectrometry includes the possibility to determine arginine levels, thus allowing for the detection of increased risk for arginase 1 deficiency . Since the overlap between normal arginine levels in affected and unaffected newborns is quite large, requiring Arg/Orn to also be elevated in order to consider a screen result as positive is a common practice for avoiding false positives . Our patient presented with slightly elevated levels of arginine on the NBS results.…”

Section: Discussionmentioning

confidence: 99%

A new metabolic disorder in human cationic amino acid transporter‐2 that mimics arginase 1 deficiency in newborn screening

Yahyaoui

Blasco‐Alonso

Benito

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

Purpose: We report a patient with a human cationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). Methods: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. Results: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-offunction mutations in the SLC7A2 gene. Currently, the child receives a proteincontrolled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. Conclusion: We identified a novel defect in human CAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening. K E Y W O R D S arginase 1 deficiency, arginine, cationic amino acid transporter-2, hyperargininemia, newborn screening

show abstract

Section: Discussionmentioning

confidence: 99%

A new metabolic disorder in human cationic amino acid transporter‐2 that mimics arginase 1 deficiency in newborn screening

Yahyaoui

Blasco‐Alonso

Benito

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Ornithine is used by one newborn screening program to screen for argininemia through the use of an arginine / ornithine ratio [16]. Glycine levels can be measured by MS/MS in the DBS sample to screen for non-ketotic hyperglycinemia (NKHG).…”

Section: Future Directionsmentioning

confidence: 99%

The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention: Thirty-Five Year Experience Assuring Newborn Screening Laboratory Quality

Jesús

Mei

Cordovado

et al. 2015

IJNS

View full text Add to dashboard Cite

Newborn screening is the largest genetic testing effort in the United States and is considered one of the ten great public health achievements during the first 10 years of the 21st century. For over 35 years, the Newborn Screening Quality Assurance Program (NSQAP) at the US Centers for Disease Control and Prevention has helped NBS laboratories ensure that their testing does not delay diagnosis, minimizes false-positive reports, and sustains high-quality testing performance. It is a multi-component program that provides comprehensive quality assurance services for dried blood spot testing. The NSQAP, the Biochemical Mass Spectrometry Laboratory (BMSL), the Molecular Quality Improvement Program (MQIP) and the Newborn Screening Translation Research Initiative (NSTRI), aid screening laboratories achieve technical proficiency and maintain confidence in their performance while processing large volumes of specimens daily. The accuracy of screening tests could be the difference between life and death for many babies; in other instances, identifying newborns with a disorder means that they can be treated and thus avoid life-long disability or severe cognitive impairment. Thousands of newborns and their families have benefited from reliable and accurate testing that has been accomplished by a network of screening laboratories and the NSQAP, BMSL, MQIP and NSTRI.

show abstract

“…A US-based newborn screening (NBS) study predicted a similar rate, estimating birth prevalence at 0.9 cases per million live births [ 9 ]. However, estimating prevalence of ARG1-D via NBS can be challenging due to the variability of arginine levels in the first days of life and since ARG1-D is not universally included on all NBS panels [ 10 ]. Arginine accumulates slowly after birth and as a result the range of levels in affected and unaffected newborns can overlap, making it difficult to determine an appropriate diagnostic threshold to accurately assess arginine deficiency in neonates [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Arginase 1 Deficiency: using genetic databases as a tool to establish global prevalence

Catsburg

Anderson

Upadhyaya³

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background/objective Arginase 1 Deficiency (ARG1-D) is a rare inherited metabolic disease with progressive, devastating neurological manifestations with early mortality and high unmet need. Information on prevalence is scarce and highly variable due to limited newborn screening (NBS) availability, variability of arginine levels in the first days of life, and high rates of misdiagnosis. US birth prevalence was recently estimated via indirect methods at 1.1 cases per million live births. Due to the autosomal recessive nature of ARG1-D we hypothesize that the global prevalence may be more accurately estimated using genetic population databases. Methods MEDLINE and EMBASE were systematically searched for previously reported disease variants. Disease variants in ARG1-D were annotated wherever possible with allele frequencies from gnomAD. Ethnicity-specific prevalence was calculated using the Hardy–Weinberg equation and applied to generate country-specific carrier frequencies for 38 countries. Finally, documented consanguinity rates were applied to establish a birth prevalence for each country. Results 133 of 228 (58%) known causative alleles were annotated with ethnic-specific frequencies. Global birth prevalence for ARG1-D was estimated at 2.8 cases per million live births (country-specific estimates ranged from 0.92 to 17.5) and population prevalence to be 1.4 cases per million people (approximately 1/726,000 people). Birth prevalence estimates were dependent on population demographics and consanguinity rate. Conclusion Birth prevalence of ARG1-D based on genetic database analysis was estimated to be more frequent than previous NBS studies have indicated. There was a higher degree of confidence in North American and European countries due to availability of genetic databases and mutational analysis versus other regions. These findings suggest the need for greater disease education around signs and manifestations of ARG1-D, as well as more widespread testing and standardization of screening for this severe disease in order to appropriately identify patients prior to disease progression.

show abstract

Case Report of Argininemia: The Utility of the Arginine/Ornithine Ratio for Newborn Screening (NBS)

Cited by 13 publications

References 2 publications

A new metabolic disorder in human cationic amino acid transporter‐2 that mimics arginase 1 deficiency in newborn screening

A new metabolic disorder in human cationic amino acid transporter‐2 that mimics arginase 1 deficiency in newborn screening

The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention: Thirty-Five Year Experience Assuring Newborn Screening Laboratory Quality

Arginase 1 Deficiency: using genetic databases as a tool to establish global prevalence

Contact Info

Product

Resources

About