Clinical laboratory standard capillary protein electrophoresis alerted of a low C3 state and lead to the identification of a Factor I deficiency due to a novel homozygous mutation.
Complement factor I (CFI) deficiency is typically associated to recurrent infections with encapsulated microorganisms and, less commonly, to autoimmunity. We report a 53-years old male who, in a routine control for non-alcoholic fatty liver disease, presented a flat beta-2 fraction at the capillary protein electropherogram. Patient's clinical records included multiple oropharyngeal infections since infancy and an episode of invasive meningococcal infection. Complement studies revealed reduced C3, low classical pathway activation and undetectable Factor I. CFI gene sequencing showed a novel inherited homozygous deletion of 5 nucleotides in exon 12, causing a frameshift leading to a truncated protein. This study points out that capillary protein electrophoresis can alert of possible states of low C3, which, once confirmed and common causes ruled out, can lead to CFI and other complement deficiency diagnosis. This is important since they constitute a still underestimated risk of invasive meningococcemia that can be greatly reduced by vaccination.
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Clara
C
Franco-Jarava
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: roger.colobran@vhir.org.
Roger
R
Colobran
Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Jaume
J
Mestre-Torres
Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain.
Victor
V
Vargas
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Ricardo
R
Pujol-Borrell
Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Manuel
M
Hernández-González
D015415:Biomarkers; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics; D003181:Complement C4; D017244:Complement Factor I / Q000235:genetics; D004252:DNA Mutational Analysis; D019075:Electrophoresis, Capillary / Q000379:methods; D030342:Genetic Diseases, Inborn / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics*; D000081208:Hereditary Complement Deficiency Diseases; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree
D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D017244:Complement Factor I
C3; Complement deficiency; Encapsulated bacterial infections; Factor I; Primary immunodeficiency; Sepsis; Serum protein electrophoresis