Manifestations of ARG1‑D often mimic those of other neurologic and neurometabolic disorders, such as other urea cycle disorders (UCDs), cerebral palsy (CP), or hereditary spastic paraplegia (HSP) 5,6
Differential diagnosis of ARG1‑D involves identifying clinical manifestations associated with high levels of plasma arginine4-7
Due to the limitations of newborn screening, ARG1‑D may be missed for numerous reasons
- Determining arginine cutoff levels in screening is problematic as the transfer of metabolites, such as arginine, from the mother to baby may compromise testing9,10
- Screening algorithms and arginine cutoff levels vary9
- ARG1‑D is not routinely a primary screening target9,11
Newborn screening for ARG1‑D is NOT available in the following 13 states9:
- South Carolina
- West Virginia
Delays in diagnosis coupled with late onset of symptoms lead to initial intervention only at ~6 years of age1
Routine testing with a
plasma amino acid panel
followed by a genetic test*
can confirm ARG1‑D12,13
Prior to initiating diagnosis, it is important to evaluate complete medical, dietary, family, and social histories and perform a thorough physical exam.
Verify high levels of arginine, which cause the manifestations
of ARG1‑D, with routine testing3,12,13
If high levels of plasma arginine are present, confirm with a genetic test*†
ARG1‑D is a rare genetic metabolic disease that requires a multidisciplinary management plan directed by a metabolic specialist.
A plasma amino acid panel and genetic test
can help diagnose ARG1‑D12,13
Elevated plasma arginine is the hallmark of ARG1‑D.3 Order a
*For plasma amino acid panel and genetic test patient eligibility criteria, please visit Order Testing.
†Due to the genetic heterogeneity of ARG1 genotypes, not all mutations causing ARG1‑D have been identified.
1. Huemer M, et al. J Inherit Metab Dis. 2016;39:331-340. 2. Edwards RL, et al. J Inherit Metab Dis. 2009;32:S197-S200. 3. De Deyn PP, et al. Hyperargininemia: a treatable inborn error of metabolism. In: Guanidino Compounds in Biology and Medicine. London, UK: John Libbey Company Ltd; 1997:53-69. 4. Burrage LC, et al. Hum Mol Genet. 2015;24:6417-6427. 5. Carvalho DR, et al. Pediatr Neurol. 2012;46:369‑374. 6. Prasad A, et al. J Child Neurol. 1997;12:301-309. 7. Crombez EA, Cederbaum SD. Mol Genet Metab. 2005;84:243-251. 8. Scaglia F, Lee B. Am J Med Genet C Semin Med Genet. 2006;142C:113-120. 9. Therell et al. Newborn screening for hyperargininemia due to Arginase 1 Deficiency. Mol Gen and Metab. 2017; 121(4):308-313. 10. Pitt JJ. Clin Biochem Rev. 2010;31:57-68. Available at: https://www.ncbi.nim.nih.gov/pmc/articles/PMC2874432/. Accessed September 14, 2021. 11. Diez-Fernandez C, et al. Hum Mutat. 2018;39:1029-1050. 12. Sun A, et al. Arginase deficiency. In: Adam MP, et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle; 2020. 13. Ah Mew N, et al. Urea Cycle Disorders Overview. 2003. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1217/. Accessed September 14, 2021. 14. Cai X, et al. Medicine (Baltimore). 2018;97:e9880. 15. Bélanger SA, et al. Paediatr Child Health. 2018;23:403-419. 16. Lüneburg N, et al. J Nutr. 2011;141:2186-2190. 17. Therell et al. Newborn screening for hyperargininemia due to arginase 1 deficiency. Mol Gen and Metab 2017;121(4):308-313.