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Progression

A progressively debilitating disease

Progress 1
  • Initial 6–12 months from birth often uneventful1,2
  • May present with1,2:
    • Seizures
    • Episodes of mild hyperammonaemia: encephalopathy, irritability, feeding difficulties, poor appetite, nausea/vomiting, decreased alertness
Progress 2
  • Spasticity in lower limbs (mainly tip-toe walking)1
  • Seizures: usually generalized tonic clonic2
    Global developmental delay:1,3 delay or developmental milestones
  • Spontaneous avoidance of high-protein foods is common1,4,5
  • Hepatic pathology: liver fibrosis, acute liver failure7
Progress 3
  • Progressive spasticity1
  • Variable decline in growth4
  • Variable decline in neuromotor and cognitive skills:1,3,5,6
    • Loss of gait
    • Decrease of vocabulary or loss of spoken language
    • Loss of sphincter control
Progress 4
  • Potential loss of:
    • Ambulation4
    • Bowel and bladder control1,7
  • Severe intellectual disability with loss of language4,8
Progress 5
  • Left untreated, ARG1-D results in variable decline that may result in early mortality1,4,8
  1. Carvalho DR, et al. Clinical Features and Neurologic Progression of Hyperarginemia. Pediatr Neurol. 2012;46:369–374.
  2. Scaglia F, Lee B. Clnical, Biochemical, and Molecular Spectrum of Hyperarginemia Due to Arginase I Deficiency. Am J Med Genet C Semin Med Genet. 2006;142:113–120.
  3. Sun A, et al. Arginase deficiency. 2004 [Updated 2020]. In: Adams MP, et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle; 2020.
  4. Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005;84:243–251.
  5. Cai X, et al. Argininemia as a cause of severe chronic stunting and partial growth hormone deficiency. Medicine. 2018;97:e9880.
  6. 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. 2018;97:e10780.
  7. Schlune A, et al. Hyperargininemia due to arginase I deficiency: the original patients and their naturalhistory, and a review of the literature. Amino Acids. 2015 Sep;47(9):1751-1762.
  8. 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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