ChediakHigashiSyndrom

Chediak-Higashi syndrome is a very rare autosomal recessive disorder caused by mutations in the LYST gene, which encodes a lysosome trafficking regulator. The mutation impairs intracellular vesicle trafficking, leading to the formation of enlarged lysosome-related organelles in multiple cell types, notably neutrophils, melanocytes, platelets, and natural killer and cytotoxic T cells.

Clinical features include oculocutaneous albinism with light hair and skin, nystagmus and photophobia; increased susceptibility to recurrent bacterial infections due to defective phagosome-lysosome fusion; and progressive neurologic deterioration such as ataxia, peripheral neuropathy, and cognitive changes. Hepatosplenomegaly and mild bleeding tendencies may be present.

Diagnosis relies on characteristic giant cytoplasmic granules in neutrophils seen on peripheral blood smear, reduced killing by NK and CTLs, and confirmation by biallelic pathogenic mutations in LYST. HLH (hemophagocytic lymphohistiocytosis) can occur and may be life-threatening.

Management focuses on preventing and treating infections, monitoring for HLH, and hematopoietic stem cell transplantation (HSCT) as the only curative option for the hematologic manifestations. HLH treatment follows established protocols (e.g., HLH-2004). Even after HSCT, neurological outcomes may be incomplete. Counseling and family planning considerations apply due to autosomal recessive inheritance.