Chediak-Higashi syndrome

Chediak-Higashi syndrome
Updated: 08/03/2020
© Jun Wang, MD, PhD

General features
  • Rare
  • Autosomal recessive
  • Lysosomal storage disorder
  • Associated with primary immunodeficiency due to impaired phagocytosis
  • Affects multiple systems
  • Symptoms usually present soon after birth
  • Most patients died before 10 as a result of infection or an accelerated lymphoma like phase
Pathogenesis
  • Abnormal intracellular protein transport and pigmentation
  • Chediak-Higashi syndrome genes (LYST/CHS1) mutation
  • Abnormal organelle trafficking and fusion
  • Defective lysosome functions
  • Neutrophils and macrophages with normal phagocytic function but delayed fusion of phagosomes with lysosomes
  • NK cell and T cell cytotoxicity markedly decreased due to defective exocytosis of granules
  • Melanosome defects
Clinical features
  • Early presentations
  • Nonpigmented skin, blonde hair, blue eyes (partial oculocutaneous albinism)
  • Recurrent bacterial infections
  • Coagulation defects, usually mild
  • Adenopathy, aphthae, gingivitis, etc
  • Progressive neurological dysfunction: peripheral neuropathy, weakness, ataxia, tremor, cranial nerve palsies, intellectual decline, etc
  • Hemophagocytic lymphohistiocytosis/accelerated phase
Key laboratory findings
  • Neutropenia
  • Markedly reduced or absent NK cytotoxicity
  • Abnormal platelet aggregation and bleeding time
  • Thrombocytopenia in accelerated phase
  • Giant granules in leukocytes, fibroblasts, Schwann cells, muscle cells, melanocytes
Genetic abnormality
  • LYST/CHS1: Non-sense or null mutation
  • No protein produced
Diagnosis
  • History: early onset of recurrent bacterial infection, partial oculocutaneous albinism
  • Lab: Giant granules in leukocytes
  • Genetic testing for LYST/CHS1
Managements


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