Chediak-Higashi Syndrome

Etiology
  • Chediak-Higashi Syndrome (CHS) is caused by a defect in proper organelle transport within cells that results in an inability of lysosomes to fuse with phagosomes. This defect affects all cells throughout the body and results in immune defects as well as pathologies which manifest in a number of tissues. Because killing of phagocytosed bacteria requires fusion of microbicidal granules with phagosomes, neutrophils and macrophages display defects in microbial killing. Furthermore, melanocytes cannot properly excrete pigment-containing melanosomes, a specialized subtype of melanocytic lysosome.
Clinical Consequences
  • Infection Susceptibility: Defective microbial killing in phagocytes causes repeated and severe bacterial infections. Albinism results from defective melanosome traficking. For less clear reasons, neutropenia and a peripheral neuropathy result.
Morphology
  • Because lysosomal granules of neutrophils cannot be unloaded into phagosomes, neutrophils display characteristic "giant granules".
Genetics
  • CHS is caused by a mutation that displays an autosomal recessive pattern of inheritance.