Chédiak-Higashi syndrome

Chédiak-Higashi syndrome (CHS), also known as Begnez-César syndrome or oculocutaneous albinism with leukocyte defects, is a rare autosomal recessive disorder caused by mutations in the LYST (lysosomal trafficking regulator) gene, also known as CHS1, located on chromosome 1q42.3. The disease affects the proper formation and function of lysosomes and lysosome-related organelles in cells throughout the body, leading to the hallmark finding of abnormally large (giant) granules in white blood cells, melanocytes, platelets, and other cell types. This fundamental cellular defect results in a multisystem disorder affecting the immune system, skin and eyes, nervous system, and blood clotting mechanisms. The classic childhood form of CHS presents with partial oculocutaneous albinism (light skin, silvery hair, and light-colored eyes with reduced pigmentation of the iris and retina), increased susceptibility to recurrent and severe bacterial infections (particularly of the skin and respiratory tract), mild bleeding tendency due to platelet dysfunction, and progressive neurological deterioration. A characteristic and life-threatening complication is the "accelerated phase," which occurs in approximately 85% of affected individuals, usually in childhood. This phase resembles hemophagocytic lymphohistiocytosis (HLH) and is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and widespread lymphocytic infiltration of organs. Without treatment, the accelerated phase is typically fatal. A milder, atypical adult form exists with primarily neurological manifestations including peripheral neuropathy, cognitive decline, and cerebellar ataxia, with less severe immunological and pigmentary abnormalities. The primary treatment for the classic form of CHS is hematopoietic stem cell transplantation (HSCT), which can correct the immunological and hematological defects and prevent the accelerated phase. HSCT is most effective when performed early, before the onset of the accelerated phase. However, transplantation does not prevent the progressive neurological deterioration that may occur over time. Supportive care includes prophylactic antibiotics to prevent infections, avoidance of sun exposure, and management of bleeding episodes. Treatment of the accelerated phase may involve immunosuppressive chemotherapy protocols similar to those used for HLH. Genetic counseling is recommended for affected families.

Common questions about Chédiak-Higashi syndrome