Researchers from India presented the case of 2 patients with arginase deficiency, 1 of whom had electroclinical features consistent with Lennox Gastaut syndrome (LGS).

“In the absence of an overt antecedent in a child with spasticity and seizure disorder, with a progressive course consistent with a developmental epileptic encephalopathy, arginase deficiency merits consideration,” the researchers wrote in a report that they published in the journal Epileptic Disorders. “Diagnosis often has important therapeutic implications with respect to dietary management and choice of the appropriate antiseizure medications.”

Read more about the diagnosis of LGS

Arginase deficiency is an under-recognized cause of pediatric developmental epileptic encephalopathies such as LGS. It is caused by a mutation in the ARG1 gene, encoding for the arginase enzyme that catalyzes the fifth and final step in the urea cycle. 

The main clinical characteristics of arginase deficiency are developmental delay or regression and spasticity, which are also observed in LGS.

Both cases presented here had biochemically confirmed arginase deficiency, including high levels of arginine and low levels of arginase in plasma. One patient also had a genetically confirmed disease.

Sodium valproate treatment led to encephalopathy and tonic status epilepticus in 1 patient and to encephalopathy with hyperammonemia in the other.

LGS is a rare but severe type of epileptic encephalopathy of childhood. It is characterized by multiple seizure types such as tonic-clonic seizures, atonic seizures, tonic seizures, myoclonic seizures, generalized nonconvulsive status epilepticus, and atypical absence seizures. The disease is also associated with specific brain wave patterns on electroencephalography and cognitive impairment, and developmental regression or delays.

In most cases, LGS is caused by a metabolic, genetic, structural, or immunological abnormality or infectious disease.

Based on the results presented here, testing for ARG1 variants should be considered in the clinical setting of LGS with spasticity and valproate intolerance.


Pavuluri H, Jose M, Fasaludeen A, et al. Arginase deficiency-an unheralded cause of developmental epileptic encephalopathy. Epileptic Disord. Published online May 27, 2023. doi:10.1002/epd2.20081