EARLY AND ACCURATE
DIAGNOSIS OF ARG1-D
IS CRUCIAL1,2

The high levels of plasma arginine, associated with ARG1-D, need to be examined beyond newborn screening and ultimately distinguish ARG1-D from cerebral palsy and hereditary spastic paraplegia3-6

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

  • Hyperammonaemia is not a hallmark of ARG1-D and acute episodes of hyperammonaemia occur infrequently4,8

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 included in newborn screening panels in a majority of the European countries11

Delays in diagnosis coupled with late onset of symptoms lead to initial intervention only at ~6 years of age1

Chart: Average manifestation of symptoms, plus mean delay in diagnosis for Arginase 1 Deficiency

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, a genetic test† can confirm the diagnosis

†Due to the genetic heterogeneity of ARG1 genotypes, not all mutations causing ARG1-D have been identified.

References:
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. Therrell BL, et al. Mol Genet Metab. 2017;121:308–313. 10. Pitt JJ. Clin Biochem Rev. 2010;31:57-68. 11. Loeber JG, Platis D, Zetterström RH et al. Int J Neonatal Screening. 2021;7:15. 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 November 26, 2021. 14. Cai X, et al. Medicine (Baltimore). 2018;97:e9880. 15. Bélanger SA, et al. Paediatr Child Health. 2018;23:403-410. 16. Lüneburg N, et al. J Nutr. 2011;141:2186-2190.