First case of homozygous C1 inhibitor deficiency.
BACKGROUND
C1 Inhibitor (C1-Inh) deficiency causes angioedema and can be hereditary (HAE), caused by mutations in the C1-Inh gene (C1NH), or acquired (AAE). Patients with HAE show a complement profile different from that of patients with AAE with normal levels of C1 (C1q, C1r, and C1s).


OBJECTIVE
We sought to characterize the complement profile of a patient with HAE and a mutation in homozygosis in the C1NH gene (c.1576T>G, Ile462Ser) and study his family.


METHODS
Biochemical diagnosis of HAE was confirmed by analyzing the C1NH gene. Further studies on the levels and activation states of the C1q, C1r, C1s, and C1-Inh components of the classical pathway of complement activation were also performed.


RESULTS
Another 7 members of the family were given diagnoses of HAE: 1 was homozygous and 6 were heterozygous for the C1NH mutation c.1576T>G. The homozygous patients showed undetectable C1q levels, reduced C1s levels, the circulating active form of C1r, and a C1-Inh mostly in its cleaved inactive form in plasma.


CONCLUSIONS
This is the first report of patients homozygous for a mutation affecting the coding region of C1NH. These patients showed a unique activation and consumption profile of the classical complement activation pathway different from that commonly observed in patients with HAE but similar to that of patients with AAE.


CONCLUSIONS
The most common HAE treatment is attenuated androgens, which increase the C1NH gene transcription levels. Because the homozygous patients lack a wild-type allele, long-term prophylactic treatment with attenuated androgens might not be advisable.
Blanch
Alvaro
A
Unidad de Inmunología, Hospital Universitario La Paz, Madrid, Spain.
Roche
Olga
O
Urrutia
Ignacio
I
Gamboa
Pedro
P
Fontán
Gumersindo
G
López-Trascasa
Margarita
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000799:Angioedema / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D003172:Complement C1 / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005796:Genes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D010375:Pedigree
D003172:Complement C1; D050718:Complement C1 Inhibitor Protein