Type III hereditary angio-oedema: clinical and biological features in a French cohort.
BACKGROUND
Hereditary angio-oedema (HAE) has been associated with C1inhibitor deficiency. The first cases of type III HAE were described in patients with normal C1Inh antigenic protein level and function and normal C4 levels in 2000. This finding has been reported mostly in women with a family history and may be influenced by exogenous oestrogen exposure.


OBJECTIVE
The purpose of this article is to describe the clinical, biological and genetic characteristics of a French population suffering from type III HAE.


METHODS
We conducted a retrospective analysis of angio-oedema (AE) cases seen in the National Reference Centre of AE between 2000 and 2009.


RESULTS
We found 26 patients (from 15 unrelated families) with type III HAE. All but four were women and presented with typical AE attacks, exacerbated by pregnancy or oral contraceptives containing oestrogens (OC). We also found that 54.5% of women were worsened with oestrogen and 23% were oestrogen dependent. All patients improved on long-term prophylactic tranexamic acid treatment; some acute attacks improved with C1Inh concentrate infusion. All of the patients had normal C1Inh and C4 levels. C1Inh function was also normal, except in women receiving OC or during a pregnancy: transient, moderately low levels (32-74% of the normal range) were found in 18 patients tested (67%). No SERPING1 gene mutation was found. Six patients from three unrelated families were heterozygous for an F12 gene variant.


CONCLUSIONS
Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence.
Vitrat-Hincky
V
V
Internal Medicine Department, University Hospital of Grenoble, Grenoble, France.
Gompel
A
A
Dumestre-Perard
C
C
Boccon-Gibod
I
I
Drouet
C
C
Cesbron
J Y
JY
Lunardi
J
J
Massot
C
C
Bouillet
L
L
D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000453:epidemiology; D015331:Cohort Studies; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D050718:Complement C1 Inhibitor Protein; D004967:Estrogens / Q000494:pharmacology; D005174:Factor XII / Q000235:genetics; D005190:Family; D005260:Female; D005602:France; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011247:Pregnancy; D012189:Retrospective Studies; D014148:Tranexamic Acid / Q000627:therapeutic use
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D004967:Estrogens; C469952:SERPING1 protein, human; D014148:Tranexamic Acid; D005174:Factor XII