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Chediak-Higashi syndrome

Authors
Robert L Roberts, MD, PhD
Kevin Yeh-Sheng Wang, MD, LAc
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by recurrent pyogenic infections, partial oculocutaneous albinism, progressive neurologic abnormalities, mild coagulation defects, and a lymphoma-like accelerated phase (MIM 214500). A mouse model of CHS, with an altered "beige" coat color, has been an important source of information on the disease [1-3]. The gene responsible for this defect was first discovered in the mouse model and is called Beige. It and the defective human gene, called CHS1/LYST, are part of the BEACH family of vesicle trafficking regulatory proteins.

The diagnosis of CHS can be made by examination of a peripheral smear for pathognomonic giant cytoplasmic granules in leukocytes and platelets. Hematopoietic cell transplantation (HCT) is the treatment of choice.

This topic will review the pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CHS. An overview of primary disorders of phagocytic function is presented separately. (See "Primary disorders of phagocytic function: An overview".)

EPIDEMIOLOGY

Chediak-Higashi syndrome (CHS) is a rare disorder. The exact incidence is unknown. Less than 500 cases have been reported worldwide in the past 20 years [1]. Parental consanguinity is common.

PATHOGENESIS

The underlying defect in Chediak-Higashi syndrome (CHS) is abnormal organellar protein trafficking that is suspected to lead to aberrant fusion of vesicles and failure to transport lysosomes to the appropriate site of action [2]. This defect is due to a mutation in the lysosomal trafficking regulator (CHS1/LYST) gene at 1q42.1-2 (MIM #214500) [3,4]. Most mutations are nonsense or null mutations, resulting in an absent CHS1/LYST protein [5]. Milder forms of CHS have been reported with missense mutations that probably encode a partially functioning protein.

        

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Literature review current through: Nov 2016. | This topic last updated: Fri Oct 23 00:00:00 GMT 2015.
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