Variable Clinical Presentation in Complement Deficiency Disorders: Single-Center Experience

Introduction Complement deficiency disorders, characterized by autoimmunity and recurrent bacterial infections, are diagnosed through complement pathway testing and genetic analysis, with management involving antibiotics, vaccination, and treating autoimmune manifestations. Presentation This case series outlines six patients with diverse presentations. First 3 patients had recurrent meningococcal infections: a 25-year-old male had meningococcal meningitis at the age of 15 and 22; a 30-year-old female had meningococcal sepsis at 10 and 19; and a 30-year-old female had meningococcal meningitis at 15 and sepsis at 22. In all three patients, terminal complement pathway deficiency was confirmed, where the first patient is homozygous for a C8B deficiency and heterozygous for C9. The second and third patients are also homozygous for C8B deficiency. Two other patients had a more complicated infectious diathesis: a 48-year-old male had pneumonia at 10, followed by sepsis at 19 and meningococcal meningitis at 47; a 53-year-old female had an episode of meningitis at the age of 1, followed by recurrent pneumonias since childhood and the development of emphysema and pulmonary arterial hypertension leading to lung transplantation. Functional analysis in the male patient showed a deficiency in all three complement pathways, but the terminal complex activity was elevated (genetic testing is pending), whereas in the female patient, a terminal complement pathway deficiency was confirmed with a homozygous variant in C2 gene. One patient had predominantly autoimmune manifestations: a 58-year-old female with systemic lupus erythematosus and thrombycytopenia. A severely reduced classical and lectin pathway was found, with low C4, C1 inhibitor, and factor B and I. Genetic testing is pending. Discussion The cases illustrate heterogeneity in complement deficiency presentations, leading to delayed diagnosis. Genetic testing remained incomplete in some patients. Early diagnosis and vigilant monitoring are crucial to reduce infection recurrence and autoimmune progression.