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01.12.2016 | Research | Ausgabe 1/2016 Open Access

Orphanet Journal of Rare Diseases 1/2016

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

Zeitschrift:
Orphanet Journal of Rare Diseases > Ausgabe 1/2016
Autoren:
Rosa Maria Dellepiane, Laura Dell’Era, Paola Pavesi, Paolo Macor, Mara Giordano, Luca De Maso, Maria Cristina Pietrogrande, Massimo Cugno
Wichtige Hinweise

Competing interest

Rosa Maria Dellepiane, Laura Dell’Era, Paola Pavesi, Paolo Macor, Mara Giordano, Luca De Maso, Maria Cristina Pietrogrande and Massimo Cugno declare that they have no conflict of interest.

Authors’ contributions

RMD, LD and PP designed the study, followed the patients, collected clinical and laboratory data, drafted the manuscript. PM carried out tests of complement activity and contributed in the interpretation of the results, contributed in writing the manuscript. MG carried out genetic analysis and contributed in the interpretation of the results, contributed in writing the manuscript. LDM carried out tests of complement activity and contributed in the interpretation of the results. MCP designed the study, followed the patients, collected clinical and laboratory data, contributed in writing the manuscript. MC designed the study, carried out functional tests for the classical, alternative and mannose-binding lectin complement pathways, contributed in writing the manuscript. All authors read and approved the final manuscript.

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.
Literatur
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