Genetic focus: long arm of chromosome 1q43 (in common form)
Inheritance: autosomal recessive
Clinical features:
(1) defect in delta-granules of platelet with a storage pool defect
(1a) large granules
(1b) mild to moderate bleeding disorder with prolonged bleeding time
(1c) decreased levels in serotonin
(1d) decrease in the ADP to ATP ratio
(1e) absent second wave of platelet aggregation
(2) partial oculocutaneous albinism with mild hypopigmentation
(2a) white forelock or ashen hair, with silver-gray sheen
(2b) uveal hypopigmentation
(2c) skin color lighter than other family members
(2d) photophobia
(2e) large melanosomes
(3) large, coarse, peroxidase-positive cytoplasmic granules in neutrophils, monocytes and lymphocytes
(3a) leukocyte dysfunction (poor mobilization from marrow, defective chemotaxis, impaired bactericidal activity)
(3b) susceptibility to bacterial infections (often Staphylococcus or Streptococcus) with pneumonia and cellulitis
(4) abnormally large cytoplasmic granules in:
(4a) renal tubular cells
(4b) gastric chief and parietal cells
(4c) hepatocytes
(4d) fibroblasts
(4e) neurons
(4f) pneumocytes
(5) immune dysfunction
(5a) lymphoproliferative disorders during the "accelerated" phase
(5b) susceptibility to Epstein-Barr viral infections
(5c) defective natural killer cell function
(6) neurologic dysfunction
(6a) polyneuropathy
(6b) ataxia
Features of the accelerated phase:
(1) proliferation of lymphocytes and histiocytes in the liver, spleen and bone marrow
(2) pancytopenia
(3) fever
(4) recurrent infections and sepsis
