Invasive meningococcal disease in three siblings with hereditary deficiency of the 8th component of complement: Evidence for the importance of an early diagnosis

Rosa Maria Dellepiane, Laura Dell'Era, Paola Pavesi, Paolo Macor, Mara Giordano, Luca De Maso, Maria Cristina Pietrogrande, Massimo Cugno

Research output: Contribution to journalArticle

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Article number64
JournalOrphanet Journal of Rare Diseases
Volume11
Issue number1
DOIs
Publication statusPublished - May 17 2016

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Keywords

  • C8 deficiency
  • Complement deficiency
  • Meningococcal disease
  • Neisseria meningitidis

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

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