A Case of Meningococcal Sepsis and Meningitis with Complement 7 Deficiency in a Military Trainee

Complement component 7 (C7) deficiency leads to the loss of complement lytic function, and affected patients show increased susceptibility to encapsulated organisms infection, especially Neisseria meningitidis. Recently, we have experienced a 20-year-old military trainee with meningococcal sepsis and meningitis who was diagnosed as having C7 deficiency based upon the undetectable serum C7 protein on radioimmunoassay. This case emphasizes that although C7 deficiency is rare immune disorder, it is important to be aware of possibility about late complement deficiency among patients who present with meningococcal disease.

A Korean familial case of hereditary complement 7 deficiency / 소아과

Meningococcal infections can be associated with abnormalities of the complement system, which contains 5 terminal complement proteins. Furthermore, deficiencies in 1 of these 5, complement component 7 (C7), leads to the loss of complement lytic function, and affected patients show increased susceptibility to recurrent meningococcal meningitis and systemic Neisseria gonorrhoeae infection. In September 2003, an 11-year-old female patient presented at our outpatient department with high fever, lower leg pain, headache, and petechiaes. She rapidly progressed to coma but later achieved full recovery due to prompt treatment. Her final diagnosis was meningococcal sepsis and arthritis. Her elder brother also had a similar bacterial meningoencephalitis history, which encouraged us to perform analyses for complement component and gene mutations. Resultantly, both the brother and sister were found to have the same mutation in the C7 gene. Subsequently, vaccinations of the meningococcal vaccine meningococcal vaccine (Menomune(R)) were administered. However, in September 2006, the brother expired due to acute micrococcus meningoencephalitis. At present, the 16-year-old female patient is healthy. Here, we report a Korean family with a hereditary C7 deficiency with susceptibility to meningococcal infections due to C7 gene mutation.

Two Novel Mutations in the C7 gene in a Korean Patient with Complement C7 Deficiency

Complement C7 deficiency is an autosomal recessive disorder well known to be associated with increased susceptibility to meningococcal infection and has mostly been reported in Caucasians. In the Korean population, no case of C7 deficiency has been reported to date. Recently we experienced an 11-yr-old girl with meningococcal meningitis who was diagnosed as having C7 deficiency based upon the undetectable serum C7 protein on radial immunodiffusion and the undetectable serum total and C7 hemolytic activities. To identify the genetic basis of the C7 deficiency of the patient, we performed a mutation analysis for the C7 gene and found two novel mutations; a point mutation at the 3'splice acceptor site of intron 4 (c.281-1G>T) and a large deletion mutation encompassing almost the whole C7 gene from exon 1 to exon 17 (c.1-?_2350+?del). A haplotype analysis showed that the large deletion mutation was inherited from the patient's father. To the best of our knowledge, this is the first confirmed case of C7 deficiency in Korea.

A Case of Hereditary C7 Deficiency Associated with Meningococcal Meningitis / 소아과

The complement system is composed of more than 25 different proteins and is usually divided into classical and alternative pathways. Complement component 7(C7) is one of the five terminal complement proteins that, upon activation of either the classical or the alternative pathway, interacts sequentially to form a large protein-protein complex, called membrane attack complex(MAC). Assembly of the MAC on target cells results in the formation of transmembrane pores that can lead to the killing of the cells. C7 deficiency is an autosomal recessive disorder that is mostly reported in Caucasians. The gene for C7 has been assigned to chromosome 5p13. To date, 15 different molecular defects leading to total or subtotal C7 deficient defects have been reported. C7 deficiency is associated frequently with recurrently bacterial infections, especially meningitis caused by Neisseria meningitidis. We report a case of a hereditary C7 deficiency associated with meningococcal meningitis.