Chediak-Higashi syndrome

Author: Brian Wu PhD. MD Candidate, Keck School of Medicine, Los Angeles, USA; Chief Editor: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, July 2016.


What is Chediak-Higashi syndrome?

Chediak-Higashi syndrome is a childhood disorder that interferes with immune system function. It is also known as Begnez-Cesar syndrome, leukocyte anomaly albinism or defect in natural killer lymphocytes.

It was first described in 1943 by Dr. Beguez-Cesar. 

Who gets Chediak-Higashi syndrome?

Chediak-Higashi syndrome is rare.

  • An estimated 200–500 cases have been reported worldwide.
  • The incidence is the same in males and females.
  • It affects all races, but researchers suspect its occurrence may be under-reported.

What causes Chediak-Higashi syndrome?

Chediak-Higashi syndrome is an autosomal recessive condition caused by a mutation on the LYST gene. It is often due to parental consanguinity. The LYST gene affects the creation and maintenance of storage granules and causes problems with the transport of protein across cells.

Genetics of Chediak-Higashi syndrome*

*Image courtesy Genetics 4 Medics

What are the clinical symptoms of Chediak-Higashi syndrome?

Signs and symptoms begin to affect children with Chediak-Higashi syndrome shortly after birth or by age five at the latest.

  • Oculocutaneous albinism, or hypopigmentation of the hair, eyes and skin; hair is described as light in colour with a metallic sheen
  • Prolonged bleeding and easy bruising due to platelet abnormalities
  • Frequent viral, bacterial and fungal infections
  • Photosensitivity
  • Nystagmus: abnormal, involuntary eye movements
  • Numbness/tingling in the limbs due to peripheral neuropathy
  • Poor immunity due to abnormal function and shape of natural killer cells

Onset of Chediak-Higashi syndrome in adult life is associated with milder symptoms. These may include:

Complications of Chediak-Higashi syndrome

The majority of patients (around 80%) will undergo an accelerated phase of Chediak-Higashi syndrome. This phase is marked by the nonmalignant reproduction of white blood cells in multiple body organs. This accelerated phase can be precipitated by the presence of a viral infection, and it is often fatal if it occurs in childhood.  This phase is called hemophagocytic lymphohistiocytosis (HLH).

How is Chediak-Higashi syndrome diagnosed?

Diagnosis of Chediak-Higashi syndrome is made by:

  • Examination of the white blood cells for the presence of large granules
  • Light microscopy of the hair to find pigment clumping  

How is Chediak-Higashi syndrome treated?

Treatment for Chediak-Higashi syndrome may include:

  • Cord blood or bone marrow transplant, considered the treatment of choice; it is more successful if done before a child reaches the accelerated phase
  • Chemotherapy is needed to put hemophagocytosis (the HLH phase) into remission before transplant can take place
  • Avoidance of exposure to sunlight and sun protective measures

What is the outlook for Chediak-Higashi syndrome?

Without treatment, the outlook for Chediak-Higashi syndrome is poor. Around 50–85% of children with this disorder will enter the accelerated HLH phase. This process with fatal without treatment and most patients will die by the age of 10 years.

 

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