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Key symptoms of ARG1-D

The clinical presentation of ARG1-D is heterogeneous1-5

Manifestations typically start in childhood, although symptoms can appear later in life due to accumulating levels of plasma arginine1

Initial onset is typically confined to the lower limbs; however, as spasticity worsens, the upper limbs can also become affected1

Persistent high plasma levels of arginine and arginine-related metabolites increase the risk of significant morbidity and early mortality1,2,6-10

Symptoms

Symptoms often mimic other neurologic and neurometabolic disorders, leading to misdiagnosis1-11

Symptoms

*Hyperammonaemia is not a hallmark of ARG1-D and acute episodes of hyperammonaemia occur infrequently3-5

  1. Carvalho DR, et al. Clinical Features and Neurologic Progression of Hyperarginemia. Pediatr Neurol. 2012;46:369-374.
  2. Crombez EA, Cederbaum SD. . Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005;84:243-251.
  3. Sin YY, et al. Arginase-1 deficiency. J Mol Med (Berl). 2015;93:1287-1296.
  4. Cai X, et al. Argininemia as a cause of severe chronic stunting and partial growth hormone deficiency .Medicine (Baltimore). 2018;97:e9880.
  5. Bakhiet M, et al. A case report of neurlogical complications owning to lately diagnosed hyperargininemia emphasizing the role of national neonatal screening policies in the kingdom of Bahrain Medicine (Baltimore). 2018;97:e10780.
  6. Diez-Fernandez C, et al. Mutations and common variants in the human arginase 1 (ARG1) gene: Impact on patients, diagnostics, and protein structure considerations. Hum Mutat. 2018;39:1029-1050.
  7. Häberle J, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 2019;1–39.
  8. 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.
  9. Sun A, et al. Arginase deficiency. In: Adams MP, et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle; 2020.
  10. Diaz GA, et al. Poster presented at: 13th European Paediatric Neurology Society (EPNS) Congress; September 17-21, 2019; Athens, Greece. Poster P06-34.
  11. Prasad A, et al. Argininemia: A Treatable Genetic Cause of Progressive Spastic Diplegia Simulating Cerebral Palsy: Case Reports and Literature Review. J Child Neurol. 1997;12:301-309.  

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