these genes are 16q24 for p22phox, 7q11.23 for p47phox, and 1q25 for p67phox. Glucose-6-phosphate dehydrogenase also is involved in the production of superoxide, and severe forms of glucose-6-phosphate dehydrogenase deficiency also result in CGD. Patients characteristically have lymphadenopathy, hypergammaglobulinemia, hepatosplenomegaly, dermatitis, failure to thrive, anemia, chronic diarrhea, and abscesses. Infections occur in the lungs, the middle ear, gastrointestinal tract, skin, urinary tract, lymph nodes, liver, and bones.
Figure 74-1 Schematic representation of neutrophil migration from the vascular space across the vascular endothelium into tissues. Neutrophils bind to selectin (Eor P-selectin) molecules on the surface of vascular endothelium via sialylated and fucosylated tetrasaccharides related to the S-LeX blood group found on the surface of neutrophils. The bound neutrophils roll along the endothelium and become tightly bound by the interaction of the adhesion molecule leukocyte function-associated antigen type 1 (LFA-1) on the neutrophil and intercellular adhesion molecule type 1 on vascular endothelium, allowing neutrophils to move through the endothelium and into the tissue spaces. (Adapted from Janeway CA, Travers P, Walport M, et al: Immunobiology: the Immune System in Health and Disease, ed 4, New York, 1999, Elsevier.)
Granulomas are prominent and may obstruct the pylorus or ureters.
Chédiak-Higashi syndrome, an abnormality of secondary granules, is an autosomal recessive disorder caused by a mutation in a cytoplasmic protein (CHS1) thought to be involved in organellar protein trafficking, resulting in a fusion of the primary and secondary granules in neutrophils. Giant granules are present in many cells, including lymphocytes, platelets, and melanocytes. Patients usually have partial oculocutaneous albinism. The defect in Chédiak-Higashi syndrome results in defective neutrophil and natural killer cell function, leading to recurrent and sometimes fatal infections with streptococci and staphylococci. Most patients progress to an accelerated phase associated with Epstein-Barr virus infection and characterized by a lymphoproliferative syndrome with generalized lymphohistiocytic infiltrates, fever, jaundice, hepatomegaly, lymphadenopathy, and pancytopenia. The condition resembles hemophagocytic lymphohistiocytosis.
The evaluation of a neutropenic child depends on clinical signs of infection, family and medication history, age of the patient, cyclic or persistent nature of the condition, signs of bone marrow infiltration (malignancy or storage disease), and evidence of involvement of other cell lines. Neutropenia is confirmed by a complete blood count and differential. A bone marrow aspirate and biopsy may be necessary to determine whether the neutropenia is due to a failure of production in the bone marrow, infiltration of the bone marrow, or loss of neutrophils in the periphery. Antineutrophil antibodies help diagnose autoimmune neutropenia.