Chédiak-Higashi syndrome: Difference between revisions

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Associated features: Abnormalities in melanocytes (albinism), nerve defects, bleeding disorders.
Associated features: Abnormalities in melanocytes (albinism), nerve defects, bleeding disorders.
 
==Historical perspective==
It is named for the [[Cuba]]n physician and serologist [[Alejandro Moisés Chédiak]] (1903-1993) and the [[Japan]]ese pediatrician [[Otokata Higashi]] (1902-1981).<ref>{{cite book |title=Neurocutaneous Disorders: Phakomatoses and Hamartoneoplastic Syndromes |chapter=Silver hair syndromes: Chediak–Higashi syndrome (CHS) and Griscelli syndromes (GS) |author=Saez-De-Ocariz M, Orozco-Covarrubias L, Duràn-McKinster C, Ruiz-Maldonado R |publisher=Springer |doi=10.1007/978-3-211-69500-5_19 |isbn=978-3-211-21396-4 |pages=407–26 |year=2008 |editor=Ruggieri M, Pascual-Castroviejo I, Di Rocco C, editors }}</ref> It is often spelled without the accent as Chediak–Higashi syndrome.
==Causes==
==Causes==
Chédiak–Higashi syndrome is caused by mutations in the [[LYST]] gene. This gene provides instructions for making a protein known as the lysosomal trafficking regulator. Researchers believe that this protein plays a role in the transport (trafficking) of materials into structures called lysosomes.
Chédiak–Higashi syndrome is caused by mutations in the [[LYST]] gene. This gene provides instructions for making a protein known as the lysosomal trafficking regulator. Researchers believe that this protein plays a role in the transport (trafficking) of materials into structures called lysosomes.

Revision as of 19:54, 27 July 2012

Chédiak-Higashi syndrome
ICD-10 E70.3 (E70.340 ILDS)
ICD-9 288.2
OMIM 214500
DiseasesDB 2351
eMedicine derm/704 
MeSH D002609

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Chédiak-Higashi syndrome is a rare childhood autosomal recessive disorder that affects multiple systems of the body, and arises from a mutation in the lysosomal trafficking regulator gene, LYST.

It is a disease with impaired bacteriolysis due to failure of phagolysosome formation. As a result of disordered intracellular trafficking there is impaired lysosome degranulation with phagosomes, so phagocytosed bacteria are not destroyed by the lysosome's enzymes.

In addition, secretion of lytic secretory granules by cytotoxic T cells is also affected.

The disease is characterised by large lysosome vesicles in phagocytes (neutrophils), which thus have poor bactericidal function, leading to susceptibility to infections, abnormalities in nuclear structure of leukocytes, anaemia, and hepatomegaly.

Associated features: Abnormalities in melanocytes (albinism), nerve defects, bleeding disorders.

Historical perspective

It is named for the Cuban physician and serologist Alejandro Moisés Chédiak (1903-1993) and the Japanese pediatrician Otokata Higashi (1902-1981).[1] It is often spelled without the accent as Chediak–Higashi syndrome.

Causes

Chédiak–Higashi syndrome is caused by mutations in the LYST gene. This gene provides instructions for making a protein known as the lysosomal trafficking regulator. Researchers believe that this protein plays a role in the transport (trafficking) of materials into structures called lysosomes. Lysosomes act as recycling centers within cells. They use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Although the lysosomal trafficking regulator protein is involved in the normal function of lysosomes, its exact role is unknown.[2]

Diagnosis

History and Symptoms

People with CHS have light skin and silvery hair, and frequently complain of solar sensitivity and photophobia. Other signs and symptoms vary considerably, but frequent infections and neuropathy are common. The infections involve mucous membranes, skin, and respiratory tract. Affected children are susceptible to gram-positive and gram-negative bacteria and fungi, with S. aureus being the most common. Neuropathy often begins in the teenage years and becomes the most prominent problem. Infections in CHS tend to be very serious and even life-threatening; few patients with this condition live to adulthood.

Most children with Chédiak–Higashi syndrome ultimately reach a stage known as the accelerated phase — the lymphoma-like-syndrome. This severe phase of the disease is thought to be triggered by a viral infection (usually the Epstein-Barr virus, EBV). In the accelerated phase, defective white blood cells divide uncontrollably and invade many of the body's organs. The accelerated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These medical problems are usually life-threatening in childhood.

Mutations have been found in the CHS1 (also called LYST) gene. The primary defect in this disease is in special granules present in skin pigment cells and certain white blood cells. For example, a granule that contains melanin is not made properly in skin, resulting in decreased skin pigmentation. A defect in granules found in certain types of white blood cells causes immune system problems.[3] Albinism is typically partial, and some patients have peripheral neuropathy.

There are several manifestations of Chediak-Hegashi syndrome as mentioned above; however, neutropenia seems to be the most common. The syndrome is also associated with oculocutaneous albinism. Persons are also prone for infections, especially with Staph. Aureus.

It is associated with periodontal disease of the deciduous dentition.

Treatment

There is no specific treatment for Chédiak–Higashi syndrome. Bone marrow transplants appear to have been successful in several patients. Infections are treated with antibiotics and abscesses are surgically drained when appropriate. Antiviral drugs such as acyclovir have been tried during the terminal phase of the disease. Cyclophosphamide and prednisone have been tried. Vitamin C therapy has improved immune function and clotting in some patients.

See also

References

  1. Saez-De-Ocariz M, Orozco-Covarrubias L, Duràn-McKinster C, Ruiz-Maldonado R (2008). "Silver hair syndromes: Chediak–Higashi syndrome (CHS) and Griscelli syndromes (GS)". In Ruggieri M, Pascual-Castroviejo I, Di Rocco C, editors. Neurocutaneous Disorders: Phakomatoses and Hamartoneoplastic Syndromes. Springer. pp. 407–26. doi:10.1007/978-3-211-69500-5_19. ISBN 978-3-211-21396-4.
  2. "Chediak–Higashi syndrome". Retrieved 2008-11-06.
  3. "Chediak–Higashi syndrome". Retrieved 2008-11-06.


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