Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review

J Child Neurol. 1997 Aug;12(5):301-9. doi: 10.1177/088307389701200502.


Argininemia, a rare autosomal recessive urea cycle disorder, is caused by a deficiency of arginase, with resulting elevated plasma arginine and ammonia levels. Reports to date have focused little on the neurology of this disorder or the efficacy of treatments. A MEDLINE search revealed 25 previously reported cases, to which we have added two brothers who presented with late onset progressive spastic diplegia. Though their degree of enzyme deficiency was comparable, the severity of their phenotypic abnormalities differed substantially. With dietary therapy, both showed improved cognitive and motor function. Late metabolic crises occurred in both, resulting in death of the less severely affected brother. Based on analysis of our clinical database, we report on the full spectrum of neurologic abnormalities seen in argininemia with particular focus on the accompanying progressive spastic diplegia and its response to treatment; progressive decline in head growth; distinctive neuroradiologic findings; and life-threatening later complications. Current and potential future therapies and long-term outcome are summarized.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Amino Acid Metabolism, Inborn Errors / complications
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Amino Acid Metabolism, Inborn Errors / therapy*
  • Amino Acids, Essential / therapeutic use
  • Arginase / blood
  • Arginine / blood*
  • Atrophy / etiology
  • Cerebellum / pathology
  • Cerebral Cortex / pathology
  • Cerebral Palsy / etiology*
  • Cerebral Palsy / therapy
  • Child
  • Child, Preschool
  • Cognition Disorders / etiology
  • Dietary Proteins / adverse effects
  • Disease Progression
  • Fatal Outcome
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperargininemia*
  • Male
  • Microcephaly / etiology
  • Models, Neurological
  • Muscle Spasticity / etiology*
  • Muscle Spasticity / therapy
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / therapy
  • Seizures / etiology
  • Treatment Outcome
  • Vomiting / etiology


  • Amino Acids, Essential
  • Dietary Proteins
  • Arginine
  • Arginase