Overview
Arginase deficiency, primarily argininemia, is an autosomal recessive disorder characterized by elevated arginine levels due to impaired arginase activity, leading to symptoms such as spasticity and potential hyperammonemia, though the latter is less common compared to other urea cycle disorders 2.Diagnosis
Elevated blood and cerebrospinal fluid levels of arginine and its catabolites (e.g., alpha-keto-delta-guanidinovaleric acid, argininic acid, alpha-N-acetylarginine) 2.
Post-mortem brain analysis may show different patterns compared to peripheral fluids 2.
Genetic testing identifying pathogenic variants in the arginase gene 2.Management
First-line: Protein restriction to manage elevated arginine levels 2.
Adjunctive treatments: Early initiation of B-complex vitamin supplementation may reduce metabolic crises and symptom severity, particularly in pediatric patients 1.
Monitoring: Regular assessment of guanidino compound levels in blood and cerebrospinal fluid to guide management 2.Special Populations
Pediatrics: Early intervention with B-complex vitamins appears beneficial in mitigating symptom severity and variability 1.
Comorbidities: No specific guidance provided in the abstracts regarding comorbidities; focus remains on managing metabolic crises and spasticity 21.Key Recommendations
Initiate B-complex vitamin supplementation early in pediatric patients with arginase deficiency to potentially reduce symptom severity and metabolic crises (Evidence: Moderate 1).
Regularly monitor levels of arginine and its catabolites in blood and cerebrospinal fluid to guide treatment adjustments (Evidence: Moderate 2).
Implement protein restriction as a primary management strategy to control elevated arginine levels (Evidence: Weak 2).References
1 Miyake CY, Ehsan SA, Zhang L, Mackenzie SJ, Azamian MS, Scott DA et al.. Early initiation of B-vitamin supplementation may reduce symptoms and explain intrafamilial variability: Insights from two sibling pairs from the TANGO2 natural history study. American journal of medical genetics. Part A 2023. link
2 Deignan JL, De Deyn PP, Cederbaum SD, Fuchshuber A, Roth B, Gsell W et al.. Guanidino compound levels in blood, cerebrospinal fluid, and post-mortem brain material of patients with argininemia. Molecular genetics and metabolism 2010. link
3 Brusdeilins M, Kühner R, Schumacher K. Purification, affinity to anti-human arginase immunoglobulin-Sepharose 4B and subunit molecular weights of mammalian arginases. Biochimica et biophysica acta 1985. link90164-3)