Whilst reduced plasma C3 is commonly observed with concomitant reduction in C4 due to classical pathway activation, for example secondary to autoimmune diseases such as systemic lupus erythematosus, low plasma C3 with relative conservation of C4 is typical of alternative pathway activation, and should always prompt further investigation for monogenic causes (19, 20). The gene discussed is C3; the disease is systemic lupus erythematosus.