Arginase deficiency (argininemia)
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A child presents with progressive spastic diplegia and intellectual disability. Unlike other urea cycle disorders, hyperammonemia is mild or absent. Plasma arginine is markedly elevated.
AR; ARG1 (arginase 1)
- Progressive spastic paraparesis (resembles cerebral palsy)
- Intellectual disability
- Seizures
- Milder/absent hyperammonemia (unlike other UCDs)
- Markedly elevated plasma arginine
- Growth restriction
- Presents later than other UCDs (1-3 years)
- On RUSP
- Newborn screening (RUSP) flags elevated arginine on tandem mass spectrometry
- Plasma amino acids: markedly elevated arginine (the diagnostic biochemistry, distinct from other urea cycle disorders)
- Reduced/absent erythrocyte arginase enzyme activity
- Confirmatory ARG1 molecular testing
- Protein restriction (especially arginine), nitrogen scavengers if needed
Arginase is the last step of the urea cycle: the first 3 urea cycle enzymes are intramitochondrial (NAGS, CPSI, OTC) and the last 3 are cytosolic (ASS1, ASL, Arginase). Arginase converts arginine to ornithine + urea.
"The spastic UCD": arginase deficiency uniquely presents with progressive spastic diplegia (resembles cerebral palsy), unlike other UCDs which present with acute hyperammonemic crises. Hyperammonemia is mild or absent.