Recurrent severe pyogenic infections revealing neutrophil-specific granule deficiency caused by a novel CEBPEsplice-region variant: a case report

Neutrophil-specific granule deficiency is an exceptionally rare autosomal recessive primary immunodeficiency caused by pathogenic variants in the CCAAT/enhancer-binding protein epsilon (CEBPE) gene. Defective neutrophil maturation results in impaired bactericidal activity and recurrent pyogenic infections, predominantly affecting the skin and soft tissues. We describe two affected siblings from a family of four carrying a previously unreported CEBPE missense substitution in the splice region (p.K170N; c.510G>C). A 37-year-old woman presented with lifelong recurrent pyogenic skin infections, including abscesses, ulcerated lesions and extensive atrophic scarring involving multiple body sites. Her brother exhibited a similar phenotype complicated by recurrent osteomyelitis, pulmonary abscesses and permanent osseous deformities. Both patients had experienced recurrent infections since early childhood and had received multiple courses of antibiotics and surgical drainage procedures before the correct diagnosis was established. Peripheral blood smear demonstrated hypogranular neutrophils with bilobed nuclei, while flow cytometry revealed aberrant CD14 expression. Genetic analysis confirmed the novel CEBPE variant in both affected siblings, establishing the diagnosis of neutrophil-specific granule deficiency.