A TODDLER WITH ALTERNATIVE PATHWAY COMPLEMENT DEFICIENCY

Abstract

Introduction Complement system is an important component of innate immunity and can be activated through the classical, alternative, and lectin pathways. Patients with complement deficiency (CD) usually present with autoimmune disorders or recurrent infections. Case Description A 3-year-old Bosnian male presented with failure to thrive and recurrent infections including otitis media, pneumonia, and croup. He had mildly dysmorphic facial features, small stature (3rd%tile for weight, 14th%tile for height), developmental delay, and cervical lymphadenopathy. Immune evaluation revealed normal levels of serum immunoglobulins (IgG, IgA, IgM, and IgE), lymphocyte subsets, protein and pneumococcal vaccine titers, total hemolytic complement (CH50), and mannose-binding lectin. He had absent alternative complement activity (AH50) on three occasions. Further investigation showed low factor B and D levels, low factor D function, absent factor B function, and low properdin. Chromosomal microarray analysis is consistent with consanguinity at a level of fourth degree mating or beyond. Antibiotic prophylaxis was initiated while additional genetic evaluation and alternative pathway complement assays are underway. Discussion Although rare, alternative pathway CD should be considered in patients presenting with recurrent infections. Evaluation requires a thorough immunologic investigation including the use of CH50 and AH50 as screening assays for CD. Absent AH50 in the context of a normal CH50 is strongly indicative of an alternative pathway defect. There is an increased likelihood of autosomal recessive disorders in our case as suggested by the chromosome analysis findings.