Chediak-Higashi syndrome

Douglas J Lanska MD FAAN MS MSPH (Dr. Lanska of the Great Lakes VA Healthcare System and the University of Wisconsin School of Medicine and Public Health has no relevant financial relationships to disclose.)
Originally released January 28, 2000; last updated April 18, 2017; expires April 18, 2020

Overview

Chediak-Higashi syndrome is a rare autosomal recessive immunological disorder with hypopigmentation, recurrent infections, bleeding, and hematological malignancy. Neurologic manifestations include a parkinsonian syndrome and peripheral neuropathy, which usually occur relatively late in the course of disease. The molecular basis of this disease is due to mutations in the LYST (CHS1) gene. Lysosome trafficking regulator (LYST) is 1 of the BEACH (Beige and Chediak-Higashi) domain-containing proteins that is involved in protein trafficking and lysosomal functions. An accelerated phase of the disease can be triggered by Epstein-Barr virus infection and by some other viruses. Bone marrow transplantation or hematopoietic stem cell transplantation can provide long-term treatment for many patients. However, progressive neurologic sequelae may not be prevented by this treatment.

Key points

 

• Genetic disorders of hypopigmentation include Chediak-Higashi syndrome, which is associated with abnormal recycling of intracellular organelles.

 

• The neurologic symptoms and signs in this syndrome include parkinsonism and peripheral neuropathy late in the course of the disease.

Historical note and terminology

Chediak-Higashi syndrome is a rare, inherited, multisystem disorder affecting the immune system, pigmentation, and the nervous system (Introne et al 2015). The first description of this disorder is attributed to Cuban pediatrician Antonio Béguez Caesar (1895-1975), but it was not until more detailed descriptions of the disease and histological findings were published that this syndrome was more widely recognized (Beguez-Cesar 1943; Steinbrinck 1948; Chediak 1952; Higashi 1954). Sato first applied the eponym of “Chediak and Higashi's disease,” recognizing the likely identity of “a new leucocytal anomaly” by Cuban physician Alejandro Moisés Chédiak (1903-1993) and “congenital gigantism of peroxidase granules” by Japanese pediatrician Otokata Higashi (1883-1981) (Sato 1955).

Chediak-Higashi syndrome belongs to diseases of the immune system associated with dysfunction of the neutrophil granulocytes and to diseases that cause hypopigmentation. This disease was initially attributed to a dysfunction of leukocytes, but now it is known to cause a general dysfunction in numerous cell types, including melanocytes (causing variable degrees of oculocutaneous albinism), neutrophils and monocytes (causing immune deficiency with susceptibility for pyogenic infections), platelets (causing prolonged bleeding), and Schwann cells (causing peripheral neuropathy). Giant cytoplasmic granular inclusions in leukocytes were described in the early original publications, but later similar large granules were noted in many other cell types (Boxer 1990). Diseases resembling Chediak-Higashi syndrome were discovered in many different species, such as mink, cow, cat, dog, killer whale, and the beige mouse, which is the most extensively studied animal model for Chediak-Higashi disease (Kahraman and Prieur 1990).

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