Recurrent infections due to specific granule deficiency

Specific granule deficiency (SGD), also known as lactoferrin deficiency or neutrophil-specific granule deficiency, is an extremely rare inherited disorder of neutrophil function that leads to recurrent, severe, and often life-threatening infections. The condition is characterized by a defect in the formation of specific (secondary) granules within neutrophils, which are a critical component of the innate immune system. These granules normally contain antimicrobial proteins such as lactoferrin, collagenase, and vitamin B12-binding proteins. Without functional specific granules, neutrophils are unable to effectively kill bacteria and fungi, leaving patients highly susceptible to infections. The disease primarily affects the immune system, with patients typically presenting in infancy or early childhood with recurrent deep-seated bacterial and fungal infections of the skin, lungs, lymph nodes, and other organs. Common pathogens include Staphylococcus aureus, enteric gram-negative bacteria, and Candida species. Characteristic laboratory findings include bilobed (Pelger-Huët-like) neutrophil nuclei and the absence of specific granules on peripheral blood smear and electron microscopy. Neutrophils also demonstrate impaired chemotaxis and reduced bactericidal activity. Specific granule deficiency is most commonly caused by biallelic mutations in the CEBPE gene (encoding CCAAT/enhancer-binding protein epsilon), a transcription factor essential for myeloid cell differentiation and granule protein expression. Treatment is primarily supportive and includes aggressive antibiotic and antifungal therapy for infections, as well as prophylactic antimicrobials to reduce infection frequency. Granulocyte colony-stimulating factor (G-CSF) has been used in some patients to improve neutrophil function. Hematopoietic stem cell transplantation (HSCT) has been considered as a potentially curative option in severe cases, though experience remains limited due to the rarity of the condition.

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