Early Versus Late Diagnosis of Complement Factor I Deficiency: Clinical Consequences Illustrated in Two Families with Novel Homozygous CFI Mutations

Clara Franco-Jarava, Elena Álvarez de la Campa, Xavier Solanich, Francisco Morandeira-Rego, Virgínia Mas-Bosch, Marina García-Prat, Xavier de la Cruz, Andrea Martín-Nalda, Pere Soler-Palacín, Manuel Hernández-González, Roger Colobran

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

© 2017, Springer Science+Business Media, LLC. The complement system is an important effector arm of innate immunity and plays a crucial role in the defense against common pathogens. But effective defense and maintenance of homeostasis requires a careful balance between complement activation and regulation. Factor I (FI) is one of the most important regulators of the complement system. Complete FI deficiency is a rare autosomal recessive disorder typically resulting in severe, recurrent infection by encapsulated bacteria. In the present study, we describe two patients from unrelated families with complete FI deficiency diagnosed at very different ages: Patient 1 is a 60-year-old man who had experienced several severe infections (pneumonia, meningitis, sepsis) since childhood, one of which caused significant and permanent neurologic sequelae. In contrast, patient 2 was diagnosed at the age of 4 years after a single infectious episode (otitis media) and through detection of a flat beta2 peak on serum protein electrophoresis. This early diagnosis of FI deficiency enabled prompt implementation of a therapeutic intervention consisting of vaccination with encapsulated bacteria and prophylactic antibiotics. The two patients had novel homozygous mutations in the CFI gene (p.Gly162Asp and p.His380Arg) that disrupted protein function. Interestingly, p.His380Arg is the first mutation described affecting a residue of the highly conserved FI catalytic triad (His380, Asp429, and Ser525). This study illustrates the importance of early versus late diagnosis of FI deficiency and, in general, highlights the clinical relevance of prompt detection of complement system deficiencies.
Original languageEnglish
Pages (from-to)781-789
JournalJournal of Clinical Immunology
Volume37
Issue number8
DOIs
Publication statusPublished - 1 Nov 2017

Keywords

  • Complement system
  • Early diagnosis
  • Factor I deficiency
  • Late diagnosis
  • Meningitis
  • Mutations
  • Pneumonia
  • Primary immunodeficiencies
  • Sepsis

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