title: Invasive meningococcal disease in three siblings with hereditary deficiency of the 8(th) component of complement: evidence for the importance of an early diagnosis.
abstract: Deficiency of the eighth component of complement (C8) is a very rare primary immunodeficiency, associated with invasive, recurrent infections mainly caused by Neisseria species. We report functional and immunochemical C8 deficiency diagnosed in three Albanian siblings who presented with severe meningococcal infections at the age of 15 years, 4 years and 17 months, respectively. The youngest suffered serious complications (necrosis of fingers and toes requiring amputation).
  
  
  
  Functional activity of the classical, alternative and mannose-binding lectin complement pathways was measured in serum from the 3 siblings and their parents (37-year-old woman and 42-year-old man). Forty healthy subjects (20 males and 20 females aged 4-38 years) served as normal controls. Serum complement factors were measured by haemolytic assays and immunoblotting. Sequence DNA analysis of the C8B gene was performed.
  
  
  
  Analyses of the three complement pathways revealed no haemolytic activity and also absence of C8beta in serum samples from all three siblings. The genetic analysis showed that the three siblings were homozygous for the p.Arg428* mutation in the C8B gene on chromosome 1p32 (MIM 120960). The parents were heterozygous for the mutation and presented normal complement activities. A 2-year follow-up revealed no further infective episodes in the siblings after antibiotic prophylaxis and meningococcal vaccination.
  
  
  
  Complement deficiencies are rare and their occurrence is often underestimated. In presence of invasive meningococcal infection, we highlight the importance of complement screening in patients and their relatives in order to discover any genetic defects which would render necessary prophylaxis to prevent recurrent infections and severe complications.
authors.affiliation: Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. rosamaria.dellepiane@policlinico.mi.it.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Dellepiane
authors.affiliation: Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Dell'Era
authors.affiliation: Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pavesi
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Macor
authors.affiliation: Department of Health Sciences, Laboratory of Genetics, University of Eastern Piedmont and Interdisciplinary Research Center of Autoimmune Diseases, Novara, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: De Maso
authors.affiliation: Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pietrogrande
authors.affiliation: Department of Pathophysiology and Transplantation, Internal Medicine, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
mesh_terms: D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003185:Complement C8 / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005820:Genetic Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000473:pathology* / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D035781:Siblings; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D003185:Complement C8; D022401:Meningococcal Vaccines; D000658:Amoxicillin
keywords: C8 deficiency; Complement deficiency; Meningococcal disease; Neisseria meningitidis