Hereditary Angioedema Type I with normal complements Authors :

Hereditary angioedema (HAE), is an autosomal immunological disease, that is characterized by repetitive diffuse non-pitting painless edema without urticaria or pruritus. HAE is a rare disease with wide range of manifestation, thus diagnosis can be easily missed. Screening for HAE should be warranted in any patient with following manifestations; recurrent self-limiting unexplained abdominal pain, recurrent attacks of angioedema with no clear cause, and personal or family history of asphyxiation due to laryngeal edema in the absence of clear cause. Complement factor 4 level is considered an good screening test for HAE. Where C4 level is very low or depleted by the abnormal C1 activity especially during acute attack. Special assay for C1 esterase inhibitor level and activity is available and can indicate if the defect is quantitative or qualitative. However, C1 esterase inhibitor assay cannot exclude HAE type III (due to factor XII mutation), since it will be normal in this case. In this report, we are describing a family with type I HAE (abnormal C1 esterase inhibitor assay) but with normal C4 level, which indicate C4 level is not the optimum screening test and definitely C1 esterase inhibitor assay should be the standard of care if available for diagnosis of HAE. Clinical Importance:  C4 level is not the optimal for screening test for HAE.  C1 esterase inhibitor assay should also be the standard of care for diagnosis of HAE type I and II.  Exploring other possible mechanisms for inhibition of C1 activity other than that mediated by C1 esterase inhibitor in certain cases. Capsule Summary: In this report, we are describing a family with type I HAE (abnormal C1 esterase inhibitor assay) but with unusual normal C4 level.