Chediak-Higashi Syndrome

Pathophysiology

1) autosomal recessive congenital condition marked by defective lysosomal granules and poor chemotaxis 2) caused by abnormal increase in fusion of lysosomes

Signs and Symptoms

1) persistent, recurrent bacterial (especially Staph aureus and Strep) and fungal infections of mucous membranes, skin, and respiratory tract 2) photophobia 3) periodontal disease 4) oculocutaneous albinism 5) peripheral neuropathy 6) variable mental retardation 7) mucosal bleeding 8) easy bruising

Characteristic Test Findings

Laboratory – 1) neutropenia 2) prolonged bleeding time 3) pancytopenia in the late accelerated phase 4) defective phagocytic cell function

Histology/Gross Pathology

1) fusion of cytoplasmic granules and giant lysosomes in leukocytes 2) melanin segregation

Associated Conditions

1) a fatal and late accelerated phase in coexisting Ebstein-Barr infection

Biochemistry

1) defect is in lysosomal transport protein 2) involved gene is CHS1 on 1q42 3) decreased responsiveness of NK cells 4) defective degranulation of neutrophil lysosomes 5) impaired chemotaxis 6) platelet dysfunction

Tips for USMLE

1) if patient is a 6 year-old girl with paler than normal skin and recurrent infections, think Chediak-Higashi 2) hallmarks are defects in chemotaxis, abnormal degranulation, neutropenia, and recurrent infections