Pneumococcal HUS in infancy masking DGKE-related thrombotic microangiopathy with secondary hemophagocytic lymphohistiocytosis.

Hemolytic uremic syndrome (HUS) in infancy may be difficult to classify because infection-associated HUS and genetic thrombotic microangiopathies (TMAs) can present with similar findings. We report a 7-month-old boy admitted with pneumonia, anemia, thrombocytopenia, and acute kidney injury. Radiologically confirmed pneumonia, elevated CRP levels, positive nasopharyngeal pneumococcal PCR testing initially suggested pneumococcal-associated HUS; however, microangiopathic hemolysis and anuria persisted despite infection control, dialysis, plasma exchange, and complement inhibition therapy. Genetic analysis subsequently revealed a homozygous DGKE mutation, establishing the diagnosis of complement-independent TMA. During follow-up, the course was further complicated by secondary hemophagocytic lymphohistiocytosis (HLH) triggered by severe inflammation and catheter-related sepsis. This case demonstrates that an apparent infectious trigger does not exclude an underlying genetic etiology in infants with TMA and highlights the importance of early genetic evaluation and awareness of hyperinflammatory complications such as HLH in patients with persistent disease activity.