Differential Diagnosis for Slightly Depressed Serum C3 and C4 in an ANA-Negative Patient

• Single Most Likely Diagnosis
  • Chronic infections or inflammation: This could be due to various chronic infections or inflammatory conditions that consume complement components, leading to their decreased levels. The absence of ANA makes autoimmune diseases like lupus less likely, but chronic infections or inflammation could still be a common cause.
• Other Likely Diagnoses
  • Post-streptococcal glomerulonephritis (PSGN): Although more commonly associated with low C3, PSGN can also have low C4 levels in some cases. The ANA negativity does not rule out this condition.
  • Membranoproliferative glomerulonephritis (MPGN): This condition can present with low levels of both C3 and C4 due to the activation of the complement system.
  • Hepatic disease: Liver dysfunction can lead to decreased production of complement components, resulting in low serum levels.
• Do Not Miss Diagnoses
  • Atypical hemolytic uremic syndrome (aHUS): Although rare, aHUS is a critical condition that can present with complement activation and consumption, leading to low C3 and C4 levels. It's essential to consider this diagnosis due to its severe prognosis and the need for specific treatment.
  • Shiga toxin-producing E. coli hemolytic uremic syndrome (STEC-HUS): Similar to aHUS, STEC-HUS can consume complement components, and its diagnosis is crucial due to its potential severity.
• Rare Diagnoses
  • C3 glomerulopathy: A rare group of disorders characterized by the dysregulation of the complement system, leading to C3 deposition in the glomeruli and low serum C3 levels. C4 can also be affected in some cases.
  • Factor H deficiency or other complement factor deficiencies: These are rare genetic disorders that affect the complement system, potentially leading to low levels of C3 and C4.
  • Cryoglobulinemia: A condition characterized by the presence of cryoglobulins (proteins that precipitate at low temperatures) in the blood, which can consume complement components and lead to their decreased levels.