Chediak-higashi Information and Courses from MediaLab, Inc.

Toxic granulation is present in the neutrophil in this slide. Notice that the granules are much smaller than those seen in the previous slide in a cell from a patient with Chediak-Higashi anomaly.

Albinism, one of the striking physical characteristics of Chediak-Higashi syndrome, is also thought to be related to the general dysfunction of cells. Albinism has been specifically related to the aggregation of melanosomes, the pigment producing cells in the body.

Neutrophil from another patient with Chediak-Higashi. Notice that the granules are large but not as darkly stained as in the previous example.

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 normal azurophilic granules form, but they fuse together to form megagranules. Later during the myelocyte stage, normal 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 are able to kill bacteria in neutrophils and monocytes; however, the process is much less effective than in normal cells in part, 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.

In 1952 Chediak (a Cuban physician) reported a childhood disorder in which abnormal cytoplasmic inclusions appeared in the neutrophils of four family members. In 1954 Higashi reported a similar abnormality in an 11-month old Japanese infant. These inclusions were identified as lysosomal in origin and found in this rare autosomal recessive disorder Death was usually related to recurrent infections or hemmorhage though now some of the affected patients live to reproduce. Ocular and cutaneous albinism, increased susceptibility to pyogenic infections, abnormal granules in neutrophils, and a bleeding tendency are prominent findings. The striking neutrophilic inclusions appear as coarse intra-cytoplasmic azurophilic granules (see photograph).These granules arise from dilated portions of the Golgi-endoplasmic reticulum lysosomal apparatus. Aleutian mink and other animals are known to have Chediak-Higashi syndrome. Azurine pelts from infected mink were once prized by coat makers.