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Chédiak-Higashi Syndrome

(Chédiak-Higashi's Syndrome)

By James Fernandez, MD, PhD, Cleveland Clinic Foundation, Department of Pulmonary, Allergy and Critical Care, The R. J. Fasenmyer Center for Clinical Immunology

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Chédiak-Higashi syndrome is a rare, autosomal recessive syndrome characterized by impaired lysis of phagocytized bacteria, resulting in recurrent bacterial respiratory and other infections and oculocutaneous albinism.

Chédiak-Higashi syndrome is a rare, autosomal recessive primary immunodeficiency disorder that involves phagocytic cell defects. The syndrome is caused by a mutation in the LYST (lysosomal trafficking regulator; 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

Clinical findings of Chédiak-Higashi syndrome include oculocutaneous albinism 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 mo.

Diagnosis

  • Genetic testing

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

  • 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.

However, unless hematopoietic stem cell transplantation is done, most patients die of infections by age 7 yr. Transplantation of unfractionated HLA-identical bone marrow after pretransplantation cytoreductive chemotherapy may be curative. Five-yr posttransplantation survival rate is about 60%.

* This is the Professional Version. *