Chediak-Higashi syndrome is a rare autosomal recessive disorder. It results from a mutation of the gene LYST, which encodes a protein with multiple phosphorylation sites. This defect causes a cellular abnormality involving the fusion of cytoplasmic granules.
Early in neutrophil maturation, standard azurophilic granules form, but they fuse to form megagranules. Later, during the myelocyte stage, standard specific granules form. The mature neutrophils contain both normal-specific granules and abnormal azurophilic granules. These large abnormal granules can be seen in the cytoplasm of neutrophils, eosinophils, basophils, monocytes, and lymphocytes.
These abnormal granules can kill bacteria in neutrophils and monocytes; however, the process is much less effective than in normal cells because these neutrophils have impaired locomotion. For these reasons, individuals with Chediak-Higashi have recurrent infections.
An accelerated lymphoma-like phase occurs, with lymphadenopathy, hepatosplenomegaly, and pancytopenia. Death often occurs at an early age.
