Hyperargininemia: 7-month follow-up under sodium benzoate therapy in an Italian child presenting progressive spastic paraparesis, cognitive decline, and novel mutation in ARG1 gene

Abstract

Background: Hyperargininemia due to mutations in ARG1 gene is an autosomal recessive inborn error of metabolism caused by a defect in the final step of the urea cycle. Common clinical presentation is a variable association of progressive spastic paraparesis, epilepsy, and cognitive deficits.

Methods: We describe the clinical history of an Italian child presenting progressive spastic paraparesis, carrying a new homozygous missense mutation in the ARG1 gene. A detailed clinical, biochemical, and neurophysiological follow-up after 7 months of sodium benzoate therapy is reported.

Results: Laboratory findings, gait abnormalities, spastic paraparesis, and electroencephalographic and neurophysiological abnormalities remained quite stable over the follow-up. Conversely, a mild cognitive deterioration has been detected by means of the neuropsychologic assessment.

Conclusions: Further longitudinal studies by means of longer follow-up and using clinical, biochemical, radiological, and neurophysiological assessments are needed in such patients to describe natural history and monitor the effects of treatments.

Keywords: ARG1 gene; cognitive decline; follow-up; hyperargininemia; progressive spastic paraparesis.