An increased concentration of
ammonia is a non-specific laboratory sign indicating the presence of potentially toxic free
ammonia that is not normally removed. This does occur in many different conditions for which
hyperammonemia is a
surrogate marker.
Hyperammonemia can occur due to increased production or impaired detoxification of
ammonia and should, if associated with clinical symptoms, be regarded as an emergency. The conditions can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. If the
urea cycle is directly affected by a defect of any of the involved
enzymes or transporters, this results in primary
hyperammonemia. If however the function of the
urea cycle is inhibited by toxic metabolites or by substrate deficiencies, the situation is described as secondary
hyperammonemia. For removal of
ammonia, mammals require the action of
glutamine synthetase in addition to the
urea cycle, in order to ensure lowering of plasma
ammonia concentrations to the normal range. Independent of its etiology,
hyperammonemia may result in irreversible brain damage if not treated early and thoroughly. Thus, early recognition of a hyperammonemic state and immediate initiation of the specific management are of utmost importance. The main prognostic factors are, irrespective of the underlying cause, the duration of the hyperammonemic
coma and the extent of
ammonia accumulation. This paper will discuss the biochemical background of primary and secondary
hyperammonemia and will give an overview of the various underlying conditions including a brief clinical outline and information on the genetic backgrounds.