Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter...

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• Deficiencies in classical terminal complement components heighten susceptibility to invasive meningococcal infections.
• Recurrent meningococcal infections necessitate a comprehensive complement system diagnostic workup.
• Primary complement deficiencies are frequently underdiagnosed due to a high index of suspicion requirement.

Purpose of the Study:

• To report a multicenter experience with novel inborn errors of the classical complement system.
• To identify genetic mutations and clinical manifestations in children with complement deficiencies.
• To emphasize the importance of early diagnosis and treatment for primary complement deficiencies.

Main Methods:

• Retrospective analysis of computerized medical records of children (<18 years) from 2012-2018.
• Genetic diagnosis using whole-exome sequencing or single-gene sequencing based on immune workup findings.
• Identification of patients with novel mutations in complement components C6-C8.

Main Results:

• Five patients (3 males) from four families with two novel mutations in complement components C6-C8 were identified.
• Clinical manifestations included meningitis, with or without meningococcemia.
• Immune workup revealed nearly absent CH50 levels, indicating a complement pathway defect.
• Diagnosis delay ranged from 0 to 30 years.

Conclusions:

• Awareness of risk factors for primary complement deficiencies is crucial, even with the first infectious episode.
• Prompt immune and genetic workup should be initiated upon suspicion of complement deficiency.
• Early diagnosis and proper treatment benefit both the patient and their family.