A 32-year-old woman presents with recurrent Neisseria meningitidis infections and a family history of complement deficiency. Which investigation is most appropriate to confirm the suspected diagnosis?

Explanation

## Investigation of Choice for Suspected Complement Deficiency ### Why CH50 Assay is the Gold Standard **Key Point:** The CH50 (total hemolytic complement) assay is the **screening test of choice** for overall complement system integrity. It detects defects in any component of the classical pathway (C1–C9) and is highly sensitive for identifying complement dysfunction. **High-Yield:** CH50 measures the ability of patient serum to lyse antibody-coated sheep red blood cells. A **low or absent CH50 indicates a complement defect** and warrants component-specific testing (C3, C4, C1q, factor B, etc.). ### Diagnostic Algorithm ```mermaid flowchart TD A[Recurrent Neisseria meningitidis infections]:::outcome --> B[Suspect complement deficiency]:::outcome B --> C[Perform CH50 assay]:::action C --> D{CH50 low/absent?}:::decision D -->|Yes| E[Component-specific levels<br/>C3, C4, C1q, factor B]:::action D -->|No| F[Consider other diagnosis]:::outcome E --> G[Identify deficient component]:::outcome ``` ### Why Each Investigation Fits Its Role | Investigation | Purpose | Timing | |---|---|---| | **CH50 assay** | Screening: detects ANY classical pathway defect | **First-line** | | **C3 & C4 levels** | Component quantification (follow-up after abnormal CH50) | After positive screening | | **CD55/CD59 flow cytometry** | Diagnoses paroxysmal nocturnal hemoglobinuria (PNH), not complement deficiency | Different disease | | **PT/aPTT** | Coagulation cascade; unrelated to complement | Not relevant | **Clinical Pearl:** Recurrent *Neisseria meningitidis* is a classic presentation of **terminal complement deficiency (C5–C9)** or **C3 deficiency**. CH50 will be abnormal in both; component-specific testing then identifies which pathway is affected. **Warning:** Do NOT confuse complement deficiency with PNH (which presents with hemolysis and thrombosis). PNH is diagnosed by CD55/CD59 flow cytometry, not complement assays.