Hereditary angio-oedema (HAE) is a rare disease associated with, and caused by, an inherited deficiency of the inhibitor of the activated first component of complement (C1-inhibitor). The disease is readily diagnosed in the laboratory by measuring C1-inhibitor levels.
Very uncharacteristically for an inherited deficiency, genetic transmission is as an autosomal dominant. The patients are therefore heterozygotes and their deficiency is incomplete; many having up to 20% of the normal amount of inhibitor.
It appears most probable that attacks are precipitated by exhaustion of local inhibitor as a result of its consumption by any of the plasma enzymes (plasmin. kininogenase, P.F./Dil as well as C1)with which the inhibitor can react. Thus, conditions associated with increased generation of any of these enzymes may predispose to relapse in HAE. In the absence of all inhibitor C1 activation proceeds autocatalytically and reacting with its substrates C4 and C2 produces a kinin-like peptide from C2 which appears to be the main mediator of the disease.
Attacks of the disease have been successfully treated by replacement of inhibitor using fresh frozen plasma as source. Effective prophylactic treatment has been obtained with ɛ-aminocaproic acid and its derivatives. These drugs inhibit the activation of the plasma proteases with which the inhibitor reacts and will thus produce an ‘inhibitor sparing’ effect in addition to themselves inhibiting CT activation.