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.
