Misdiagnosis of hereditary angio-oedema type 1 and type 2

Background Hereditary angio-oedema is a rare, life-threatening, autosomal dominant condition caused by deficiency (type 1) or dysfunction (type 2) of complement C1 inhibitor. Serological assays to measure C1 inhibitor concentration and function are widely available. However, expert interpretation may not be. Objective To review all cases within three NHS Trusts with a putative diagnosis of hereditary angio-oedema. Method Review of laboratory results and clinical notes of 44 cases of presumed hereditary angio-oedema. Results Audit revealed that 11 of 42 (26%) cases had been incorrectly considered to have a diagnosis of hereditary angio-oedema. Two of 44 had insufficient data to assess. All 11 had low functional C1 inhibitor recorded at presentation. Results available in these 11 cases at the time of diagnosis showed a normal or borderline C4 level (greater than or equal to 50% of mean normal, in contrast to hereditary angio-oedema, where C4 was less than 40% of mean normal) indicating that the low C1 inhibitor levels were a result of sample decay. Cases incorrectly diagnosed were predominantly female and had a mean age at presentation of 40 years (compared with 22 years for type 1 hereditary angio-oedema). Six of the 11 cases were offered C1 inhibitor concentrate (pooled plasma product) as treatment. Conclusions We recommend that all suspected cases of hereditary angio-oedema are reviewed, that specialist advice is sought before making the diagnosis and that the diagnosis is only made after initial abnormal serology is confirmed on a second sample.