Disorders leading to an impairment of the urea cycle and hyperammonemia

Abstract Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysis of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and two transporters). The hallmark of urea cycle (UC) dysfunction is hyperammonemia, due to the impossibility of detoxifing ammonia derived from dietary protein intake, muscle catabolism or bacterial production within the intestine. Beside primary defects of one of the enzymes or transporters, other genetic or acquired conditions can secondary affect, by different mechanisms, UC function, hereby leading to hyperammonemia. Aim of this paper is to review the most important genetic conditions responsible of UC function impairment, to highlight the connection with UC enzymes and to provide the clue for differential diagnosis.