NIH

Zebra of the Week: Arginase deficiency

February 27, 2026

Argininemia is a rare, autosomal recessive urea cycle disorder caused by pathogenic variants in ARG1, resulting in deficient arginase activity and impaired conversion of arginine to urea and ornithine. Disruption of the urea cycle can lead to hyperammonemia, contributing to metabolic decompensation. Clinical manifestations commonly include feeding difficulties, vomiting, poor linear growth, seizures, and spasticity with hyperreflexia. Affected individuals may also experience developmental delay, regression of previously acquired skills, and varying degrees of intellectual disability. Management typically involves a protein‑restricted diet formulated with the guidance of a registered metabolic dietitian, alongside ongoing metabolic monitoring to mitigate hyperammonemia and support neurodevelopmental outcomes. Although prevalence estimates vary, argininemia is exceptionally uncommon, occurring in approximately 1 in 300,000 to 1,000,000 individuals worldwide.

Sources:

(Accessed 2026, February 26). NIH Genetic and Rare Diseases Information Center (GARD). Arginase deficiency. https://rarediseases.info.nih.gov/diseases/5840/arginase-deficiency

(Accessed 2026, February 26). NIH Medline Plus. Arginase deficiency. https://medlineplus.gov/genetics/condition/arginase-deficiency/#frequency