Phenotypic Pleiotropy in Arginase Deficiency: A Single Center Cohort

Area of Science:

• Biochemistry
• Genetics
• Pediatric Neurology

Background:

• Arginase deficiency is a rare urea cycle defect often misdiagnosed as diplegic cerebral palsy due to its varied presentation.
• Its rarity and slow progression make it a unique entity among urea cycle disorders.

Purpose of the Study:

• To delineate the diverse phenotypic spectrum of arginase deficiency in children.
• To highlight key clinical and biochemical markers for early identification.

Main Methods:

• Retrospective analysis of 11 children (<18 years) with diagnosed arginase deficiency (May 2011-May 2022).
• Data included clinical presentation, laboratory findings, neuroimaging, EEG, and molecular studies.
• Management involved arginine restriction and medical therapies.

Main Results:

• All patients exhibited motor delays; 81.8% experienced metabolic decompensation with encephalopathy.
• Pyramidal signs were universal, and seizures occurred in all children, with some developing epileptic encephalopathies.
• Elevated ammonia and arginine levels, along with specific neuroimaging findings, were consistently observed.

Conclusions:

• Clinical suspicion for arginase deficiency should be raised by spastic diparesis, recurrent encephalopathy, family history, and high serum arginine.
• Atypical presentations, including frequent metabolic crises and epileptic encephalopathy, were noted.
• Prompt diagnosis and intervention are essential for optimal neurodevelopmental outcomes.