Phenotypic Pleiotropy in Arginase Deficiency: A Single Center Cohort

Arginase deficiency is considered a masquerader of diplegic cerebral palsy. The rarity of hyperammonemic crisis and the slowly progressive course has made it a unique entity among the urea cycle defects.

The aim of our study is to describe the varied phenotypic spectrum of children with arginase deficiency.

This retrospective study included children and adolescents aged <18 years with a biochemical or genetic diagnosis of arginase deficiency from May 2011 to May 2022. Data were collected from the hospital's electronic database. The clinical presentation, laboratory parameters at baseline and during metabolic decompensation, neuroimaging, electroencephalography findings, and molecular studies were analyzed.

About 11 children from nine families with biochemically or genetically proven arginase deficiency were analyzed. The male: female ratio was 2.7:1. Consanguineous parentage was observed in all children. The median age at presentation was 36 months (Range: 5 months-18 years). All children with onset of symptoms in early childhood had a predominant delay in motor milestones of varying severity. Metabolic decompensation with encephalopathy occurred in all except two children (n = 9, 81.8%). Pyramidal signs were present in all patients and additional extrapyramidal signs in two children. Positive family history was present in four probands. Seizures occurred in all children. Epilepsy with electrical status in slow wave sleep and West syndrome was noted in three children. All children had elevated ammonia and arginine at the time of metabolic crisis. The spectrum of neuroimaging findings includes periventricular, subcortical, and deep white matter signal changes and diffusion restriction. The mean duration of follow-up was 38.6 ± 34.08 months. All patients were managed with an arginine-restricted diet and sodium benzoate with or without ornithine supplementation.

Spastic diparesis, recurrent encephalopathy, presence of family history, and elevated serum arginine levels must alert the clinician to suspect arginase deficiency. Atypical presentations in our cohort include frequent metabolic crises and epileptic encephalopathy. Early identification and management will ensure a better neurodevelopmental outcome.