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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Contents

Pathology notes Jun Wang, MD, PhD 1. General information Frequently discussed syndromes Terms of dermatology Terms of hematology 2. Primary immunodeficiency disorders 3. Hemodynamic abnormalities Shock Thrombosis and embolism Bleeding disorders 4.  Benign blood cell disorders Anemia Benign white cell disorders 5. Hematopoietic neoplasms Lymphoid neoplasms Myeloid neoplasms Histiocytic neoplasms: Langerhans cell histiocytosis 6. Cardiovascular system Pulmonary hypertension Cardiovascular system tumors 7. Respiratory tract tumors 8. Gastrointestinal tract Congenital disorders Infectious gastroenteritis Oral cavity Esophagus Stomach Intestinal tumors Salivary glands Exocrine pancreas and gallbladder 9. Urinary system Kidney masses Lower urinary tract 10. Male reproductive system 11. Female genital tract 12. Breast 13. Endocrine organs Pituitary gland Adrenal gland Thyroid gland Parathyroid gland Endocrine pancreas M
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Anemia

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Practice questions Anemia I

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Practice questions Anemia I © Jun Wang, MD, PhD   Abbreviations: Hb: hemoglobin HCT: hematocrit MCV: Mean Corpuscular Volume MCHC: Mean Corpuscular Hemoglobin RDW: Red Cell Distribution Width TIBC: total iron binding capacity   1. Use this case for the next three questions . A 25-year-old woman is brought to the emergency department 2 hours after being involved in a motor vehicle accident. She is conscious but feels dizziness and weakness.   Her blood pressure is 90/60 mmHg, and her heart rate is 120 beats per minute. Physical examination reveals pale skin and mucosa and a 15 cm laceration on her left thigh with significant bleeding. What are most likely the CBC and TIBC results? A. Low Hb, low HCT, high MCV, high RDW, high TIBC B. Low Hb, low HCT, slightly low MCV, normal RDW, normal TIBC C. Low Hb, low HCT, slightly high MCV, normal RDW, normal TIBC D. Normal Hb, normal HCT, normal MCV, normal
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