(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .)
Chédiak-Higashi syndrome is a rare, autosomal recessive primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves phagocytic cell defects Phagocytic cell defects Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . The syndrome is caused by a mutation in the LYST (lysosomal trafficking regulator; also known as CHS1) gene. Giant lysosomal granules develop in neutrophils and other cells (eg, melanocytes, neural Schwann cells). The abnormal lysosomes cannot fuse with phagosomes, so ingested bacteria cannot be lysed normally.
Symptoms and Signs of Chédiak-Higashi Syndrome
Clinical findings of Chédiak-Higashi syndrome include oculocutaneous albinism Pathophysiology Oculocutaneous albinism is an inherited defect in melanin formation that causes diffuse hypopigmentation of the skin, hair, and eyes. Ocular albinism affects the eyes and usually not the skin... read more and susceptibility to recurrent respiratory and other infections.
In about 80% of patients, an accelerated phase occurs, causing fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia, bleeding diathesis, and neurologic changes. Once the accelerated phase occurs, the syndrome is usually fatal within 30 months.
Diagnosis of Chédiak-Higashi Syndrome
Neutropenia, decreased natural killer–cell cytotoxicity, and hypergammaglobulinemia are common. A peripheral blood smear is examined for giant granules in neutrophils and other cells; a bone marrow smear is examined for giant inclusion bodies in leukocyte precursor cells.
The diagnosis of Chédiak-Higashi syndrome can be confirmed with genetic testing for LYST mutations.
Because this disorder is extremely rare, there is no need to screen relatives unless clinical suspicion is high.
Treatment of Chédiak-Higashi Syndrome
Supportive care using antibiotics, interferon gamma and sometimes corticosteroids
Hematopoietic stem cell transplantation
Prophylactic antibiotics can help prevent infections, and interferon gamma can help restore some immune system function. Pulse doses of corticosteroids and splenectomy sometimes induce transient remission of Chédiak-Higashi syndrome.
However, unless hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more is done, most patients with Chédiak-Higashi syndrome die of infections by age 7 years. Transplantation of unfractionated human leukocyte antigen (HLA)-identical bone marrow after pretransplantation cytoreductive chemotherapy may be curative. Five-year posttransplantation survival rate is about 60%.