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.

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.

Executive functions and cerebellar development in children.

This article examines the role of the cerebellum in processing executive functions in developmental age. The areas implicated in its elaboration are interconnected in a network that includes the prefrontal cortex, the basal ganglia, and the cerebellum. Implementation of the capacities to plan and to control corresponds to the development of the network and its structures. The development, from an evolutionary point of view, of the most recent parts of the cerebellum and of its connections with the prefrontal cortex is tied to the crucial role that it plays in an inexorable way in action execution with implicit mechanisms of anticipation and control. Deficits in executive functions are present in many cerebellar pathologies and there is also an important link between motor development and the development of many higher-order cognitive and functional domains. Further studies are needed to clarify the role of the cerebellum in executive functions both in pathological or normal conditions in the developmental age.