Fine structural studies of leukocytes from patients and heterozygotes with the Chediak-Higashi syndrome.

T HE CHEDIAK-HIGASHI SYNDROME (CR5) is characterized by large abnormal cytoplasmic organelles in cells including leukocytes which contain lysosome-like structures. This rare disease is inherited as an autosomal recessive disorder, and the clinical features include partial oculocutaneous albinism, frequent and severe pyogenic infections, and the development of a lymphoma-like ( accelerated ) phase, with pancytopenia, hepatosplenomegaly, lymphadenopathy, and widespread mononuclear cell infiltrates.’ Affected patients usually die in early childhood with pyogenic infections, or less commonly, hemorrhage.2 Based on morphologic and histochemical studies of peripheral blood leukocytes, some investigators have considered the large abnormal granules or “inclusions” to be giant lysosomes.3’4 Such morphologic abnormalities are also present in cells from the Aleutian mink ( CHS mink ) , a strain of partial albino Hereford cattle ( CHS cattle ) ,6 and a strain of Beige mice ( CHS mice ) . Similar abnormal organeiles have been observed in the skin, ocular pigment epithelium, hair,8 peripheral nerve,” scent glands, adrenal, pituitary and the organs of the GI tract of affected animals or children. Fine structural studies of the Chediak-Higashi syndrome in man have been limited. A systematic fine structural study of peripheral blood leukocytes from four patients with the Chediak-Higashi syndrome, their parents ( heterozygotes ) , and siblings was undertaken. Particular emphasis has been placed on the pleomorphic substructure of the abnormal lysosome-like organelles, their frequency and distribution, and their presence in the heterozygous state.