The Chediak-Higashi syndrome: cytoplasmic sequestration in circulating leukocytes.

By JAMES C. WHITE A RARE FAMILIAL DISORDER characterized cytologically by enormous particles in all varieties of leukocytes has been reported from various parts of the world and is known in this country as the Chediak-Higashi (C.H.) syndrome.1-4 The variable clinical manifestations of patients with this disease have included defective pigmentation, neuropathies, lymphadenopathy, hepatosplenomegaly, leukopenia, thrombocytopenia, marked susceptibility to recurrent infection, and early death due often to lymphoma. Recent investigations utilizing electron microscopy and ultrastructural cytochemistry demonstrated that the characteristic massive leukocyte granulations are giant The ease with which substrates, capture ions, and fluorescent dyes entered the large particles, and their tendency to undergo internal degeneration, indicated that C.H. granules may be abnormal lysosomes.1 Virus-like particles present in degenerating massive granules of leukocytes from two patients with C.H. syndrome suggested further that the massive lysosomes may be functionally abnormal and may conceivably l)e involved in the pathogenesis of recurrent infections afflicting these patients.11 In the course of these studies into the nature of the C.H. granulation anomaly, another unusual process was observed in peripheral leukocytes of three patients with the disorder. Small, electron-dense particles, identical to normal leukocyte lysosomal granules, were frequently observed in circular arrangements around areas of C.H. cell cytoplasm. Union of the membranes of individual granules yielded partial or complete circular profiles enclosing cytoplasmic elements. The double-walled organelles formed in this unusual manner appeared to be sequestration vacuoles. Selective staining of the rings of fused particles by the enzyme reaction product of acid phosphatase activity, and numerous examples in which tile enclosed contents appeared to be in various stages of degeneration, have suggested that sequestration leads to digestion