Four cases of Chédiak-Higashi syndrome

DOI: 10.5581/1516-8484.20110084 Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder, with fewer than 500 cases published over the last 20 years.(1) The clinical features of this syndrome include partial oculocutaneous albinism, photosensitivity, grayish hair and skin,(1,2) severe recurrent bacterial infections, bleeding diathesis and neurological manifestations (central and peripheral neuropathies, sensory loss, muscle weakness, cerebellar ataxia and cognitive impairment).(1,3) Mutations in the CHS1 (LYST) gene, located on the long arm of chromosome 1, result in a defect in granule morphogenesis in multiple tissues.(2) This gene encodes a protein called the lysosomal trafficking regulator(3) which regulates the synthesis, transport and fusion of cytoplasmatic vesicles.(4) The abnormalities observed in these vesicles result in grossly enlarged and nonfunctional lysosomes, which are identified at cytology as giant coalesced azurophilic granules present particularly in granulocytes and monocytes but also in fibroblasts, melanocytes, astrocytes, Schwann cells and hematopoietic cells.(3) These granules are specific to CHS and their presence in granulocytes from peripheral blood or bone marrow is the basis for diagnosis.(4) Patients are usually diagnosed at around the age of 5 years old. Two presentations of the disease have been described: childhood and adult.(5) Approximately 85% of the patients with the childhood form of the disease present the 'accelerated phase', characterized by lymphohistiocytic infiltration of liver, spleen, lymph nodes and bone marrow leading to fever, hepatosplenomegaly, lymphadenopathy and pancytopenia.(5) Without early hematopoietic stem cell transplantation (HSCT), most of these patients die in the first decade of life due to the accelerated phase or severe infections.(5,6) The adult form is characterized by less severe clinical manifestations and neurological impairment may be the most prominent feature.(5,6) We reviewed four patients with CHS referred to the Blood Marrow Transplantation Department of the Hospital de Clínicas, Universidade Federal do Paraná. The diagnosis of CHS was made on the basis of clinical characteristics and identification of the pathognomonic giant azurophilic granules in peripheral blood and bone marrow, which were seen in the cytoplasms of neutrophils, monocytes, eosinophils and lymphocytes (Figures 1 & 2). Three patients presented with the childhood form of the disease with two of them being referred in the accelerated phase.