Pathology Notes

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 Aden

Practice questions Benign white cell disorders © Jun Wang, MD, PhD 1. Use this case for next two questions . A 1-year-old white boy presents with recurrent pharyngitis for 4 months. His past history is otherwise unremarkable. Physical examinations reveal normal development. His weight and height are about 65 percentile. No significant abnormalities are seen except redness of his pharynx and bilateral tonsillar swollen. Laboratory tests reveal normal range hemoglobin and platelets. His absolute neutrophil count is 400/mm 3  (normal > 1500/ mm 3 ). Quantity of other white cells are within normal range. Peripheral blood smear reveal no significant morphological atypia. Bone marrow biopsy reveal normal cellularity with trilineage maturation. No dysplasia is identified. What is the most likely diagnosis? A. Autoimmune neutropenia B. Benign ethnic neutropenia C. Megaloblastic anemia D. Myelodysplastic syndrome E. Myeloproliferative neoplasm 2.   A 1-year-old white

Practice questions answers Benign white cell disorders © Jun Wang, MD, PhD 1. A. This case is characterized by neutropenia with increased risk of infection, as shown in this patient with recurrent pharyngitis. Benign ethnic neutropenia is seen in some African descendent and does not carry an increased risk for infection. Absence of morphological atypia, dysplasia and anemia make it unlikely to be megaloblastic anemia, or myelodysplastic syndrome (MDS) . Myeloproleferative neoplasms (MPN) are characterized by peripheral cytosis, not cytopenia. 2. B. Autoimmune neutropenia is likely associated with autoantibodies againt human neutrophil antigen 1. Abnormal activation of tyrosine kinases can be associated with variable disorders, including MPN . Folate acid and vitamin B12 deficiency are associated megaloblastic anemia. Single nucleotide polymorphism at Duffy antigen receptor is seen in benign ethnic neutropenia . Ineffective hematopoiesis of stem cells are associated wit