ChediakHigashi

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder of lysosomal trafficking caused by mutations in the LYST gene (also called CHS1). The condition affects multiple cell types and disrupts the formation and function of lysosome-related organelles.

Clinical features typically appear in infancy or early childhood and include partial oculocutaneous albinism with pale hair and skin, blue or gray irises, nystagmus, and photophobia.

Hematologic abnormalities include giant granules in granulocytes and other leukocytes, as well as enlarged lysosomes in melanocytes and platelets with defective dense granules. These changes impair vesicle trafficking, phagocytosis, and platelet function, contributing to infections and bleeding tendencies.

Immunologic impairment involves reduced natural killer cell and cytotoxic T lymphocyte cytotoxic function due to abnormal granule exocytosis, leading to increased susceptibility to bacterial, viral, and fungal infections.

A major complication is the accelerated phase, or hemophagocytic lymphohistiocytosis (HLH), characterized by fever, hepatosplenomegaly, cytopenias, hyperferritinemia, and potential organ failure.

Diagnosis is based on clinical features, the presence of giant lysosome-containing leukocytes on peripheral smear, and confirmation by genetic testing for LYST mutations.

Treatment includes aggressive infection management and HLH-directed therapy when HLH occurs. Hematopoietic stem cell transplantation is the only curative option and is recommended in eligible patients, ideally before or early in the HLH risk period; supportive and multidisciplinary care is essential.