Metabolic and Genetic Liver Diseases: Urea Cycle Defects

Abstract

The urea cycle is series of enzymatic reactions converting highly toxic ammonia into less toxic urea. Ammonia is a ubiquitous byproduct of amino acid metabolism. The urea cycle takes place exclusively in the liver. Although ammonia can be toxic to all tissues, brain is the most prominent target of ammonia toxicity. Acute encephalopathy is associated with astrocyte edema without axonal damage. Severe or prolonged hyperammonemia ultimately leads to progressive irreversible changes in the brain characterized by cortical and brain stem gliosis and neuronal atrophy. Management of urea cycle defects revolves around nitrogen metabolism. Clinicians should monitor nitrogen intake (protein, amino acids), nitrogen retention (appropriate growth), and nitrogen excretion (ammonia, glutamine). Ammonia scavengers can be used in the treatment of acute hyperammonemia.