ABSTRACT
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by partial oculocutaneous albinism (OCA), increased susceptibility to infection, a mild bleeding tendency, and/or late-onset progressive neurological impairment. In its classic form (classic CHS), affected children develop severe infectious or hematologic complications, including fatal hemophagocytic lymphohistiocytosis (so called accelerated phase) and possible lymphoma. In its atypical or milder form (atypical CHS), affected adolescents and adults have mild to moderate hematologic and infectious abnormalities, with later development of neurological anomalies. The pathogenesis of CHS is attributed to biallelic mutations in the CHS1 gene that encode lysosomal trafficking regulator protein, leading to the formation of giant lysosomes or lysosome-related organelles in several cell types, and subsequent impairment in the function of cytotoxic lymphocytes and natural killer (NK) cells. Diagnosis of CHS requires fulfilling a number of clinical criteria (including observation of pathognomic giant inclusions in neutrophils and lymphocytes). Molecular detection of CHS1 pathogenic variants provides further confirmation of CHS. While allogenic hematopoietic stem cell transplantation (HSCT) offers a highly effective treatment for hematologic and immune defects in affected patients, efficient therapies for neurologic anomalies are currently lacking.
