Chédiak-Higashi syndrome: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
(41 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
{{SI}}
{{CMG}} '''Assosciate Editor(s)-In-Chief:''' [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]]; {{RT}}
'''For patient information on this page, click [[Chédiak-Higashi syndrome (patient information)|here]]'''
{{SK}} Oculocutaneous albinism with leukocyte defect; Beguez Cesar disease; Chediak-Steinbrinck-Higashi Syndrome; leukocytic anomaly albinism
{{Infobox_Disease |
{{Infobox_Disease |
   Name          = {{PAGENAME}} |
   Name          = {{PAGENAME}} |
Line 9: Line 17:
   OMIM          = 214500 |
   OMIM          = 214500 |
   MedlinePlus    = |
   MedlinePlus    = |
   eMedicineSubj  = derm |
   eMedicineSubj  = |
   eMedicineTopic = 704 |
   eMedicineTopic = |
   MeshID        = D002609 |
   MeshID        = D002609 |
}}
}}


{{SI}}
==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 arises from a [[microtubule]] polymerization defect which leads to a decrease in [[phagocytosis]].  The decrease in phagocytosis results in recurrent [[pyogenic]] infections, partial albinism, and peripheral neuropathy.


{{CMG}}
==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.


{{EH}}
==Classification==


==Overview==
==Pathophysiology==
'''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]].
Chediak-Higashi syndrome 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]].  
 
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.  
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]].
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]].
Most children with Chédiak–Higashi syndrome ultimately reach a stage known as the accelerated phase &mdash; 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.
'''Associated features''':
* Abnormalities in melanocytes ([[albinism]])
* Nerve defects
* Bleeding disorders
* Periodontal disease of deciduous dentition
===Genetics===
Chediak-Higashi syndrome is [[inherited]] in a [[autosomal recessive]] pattern.


==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]].
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
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.<ref>{{ cite web |url=http://ghr.nlm.nih.gov/condition=chediakhigashisyndrome |
role is unknown.<ref>{{ cite web |url=http://ghr.nlm.nih.gov/condition=chediakhigashisyndrome |
title=Chediak–Higashi syndrome | accessdate=2008-11-06 }}</ref>
title=Chediak–Higashi syndrome | accessdate=2008-11-06 }}</ref>
==Differentiating {{PAGENAME}} from Other Diseases==
==Epidemiology and Demographics==
==Risk Factors==
==Screening==
==Natural History, Complications and Prognosis==
===Natural History===
===Complications===
* Life threatening [[infections]]
* [[Pyodermas]] and deep [[abscesses]]
* [[Neuropathy]] - begins in the teenage years
* Life threatening [[bleeding]]
* Loss of vision
* [[Renal failure]]
* Frequent infections especially with [[Epstein-Barr virus]]
* Lymphoma-like cancer
* Early death
===Prognosis===
[[Death]] often occurs in the first 10 years of life, from chronic infections or accelerated disease that results in lymphoma-like illness. However, some affected children have survived longer.
==Diagnosis==
==Diagnosis==
===Diagnostic Criteria===
===History and Symptoms===
===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.
Patients with Chediak-Higashi syndrome usually present with thefollowing symptoms:
* [[Dizziness]]
* [[Weakness]]
* [[Photophobia]]
* [[Tremor]]
* Photosensitive skin
* [[Neuropathy]]
* Frequent infections - [[Staphylococcus aureus]]
* [[Numbness]]
* [[Seizures]]
* Unsteady walking ([[ataxia]])
* Nosebleeds or easy [[bruising]]
* Intellectual disability ([[mental retardation]])


Most children with Chédiak–Higashi syndrome ultimately reach a stage known as the accelerated phase &mdash; 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.
===Physical Examination===
====Skin====
* [[Hypopigmentation skin]] ([[albinism]]) - partial
* Silvery hair


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
====Eye====
defect in granules found in certain types of white blood cells causes immune system problems.<ref name="medline">{{cite web |url=http://www.nlm.nih.gov/medlineplus/ency/article/001312.htm | title =
* [[Nystagmus]]
Chediak–Higashi syndrome | accessdate=2008-11-06 }}</ref> [[Albinism]] is typically partial, and some patients have [[peripheral neuropathy]].


==Clinical findings==
====Abdomen====
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 [[Albinism|oculocutaneous albinism]]. Persons are also prone for infections, especially with Staph. Aureus. 
* [[Hepatomegaly]]
* [[Splenomegaly]]


Associated features: Abnormalities in melanocytes (albinism), nerve defects, bleeding disorders.
====Neurologic====
* [[Neuropathy]]
 
===Laboratory Findings===
* Complete blood count and differential count - reveal [[neutropenia]], [[thrombocytopenia]]
* [[Hypergammaglobulinemia]]
* [[Bleeding time]] - prolonged
* Liver function tests - elevated [[bilirubin]]
* Peripheral blood smear - giant granules in neutrophils, eosinophils, and granulocytes are seen when examined using light microscopy.
* Bone marrow smear - peroxidase positive giant inclusion bodies in leukocyte precursor cells. The inclusion bodies contain lysosomal enzymes.
* Fluorescence cytometric analysis of leukocyte granules
 
===Imaging===
====CT====
* Brain and spinal cord atrophy
 
====MRI====
* Brain and spinal cord atrophy
 
====EMG====
* Delayed nerve conduction
 
====EEG====
* May reveal [[seizure]] activity


==Treatment==
==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
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.
terminal phase of the disease.  [[Cyclophosphamide]] and [[prednisone]] have been tried. [[Vitamin C]] therapy has improved immune function and clotting in some patients.
===Medical therapy===
 
===Surgery===
 
===Prevention===
Genetic counseling is recommended before becoming pregnant if you have a family history of Chediak-Higashi.


==See also==
==See also==
Line 59: Line 149:
{{Reflist|2}}
{{Reflist|2}}


[[Category:Pediatrics|Chediak-Higashi syndrome]]
[[Category:Pediatrics]]
[[Category:Dermatology|Chediak-Higashi syndrome]]
[[Category:Dermatology]]
[[Category:Rare diseases|Chediak-Higashi syndrome]]
[[Category:Disease]]
[[Category:Albinism|Chediak-Higashi syndrome]]
[[Category:Endocrinology]]
<br>


{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 16:32, 22 July 2016

WikiDoc Resources for Chédiak-Higashi syndrome

Articles

Most recent articles on Chédiak-Higashi syndrome

Most cited articles on Chédiak-Higashi syndrome

Review articles on Chédiak-Higashi syndrome

Articles on Chédiak-Higashi syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Chédiak-Higashi syndrome

Images of Chédiak-Higashi syndrome

Photos of Chédiak-Higashi syndrome

Podcasts & MP3s on Chédiak-Higashi syndrome

Videos on Chédiak-Higashi syndrome

Evidence Based Medicine

Cochrane Collaboration on Chédiak-Higashi syndrome

Bandolier on Chédiak-Higashi syndrome

TRIP on Chédiak-Higashi syndrome

Clinical Trials

Ongoing Trials on Chédiak-Higashi syndrome at Clinical Trials.gov

Trial results on Chédiak-Higashi syndrome

Clinical Trials on Chédiak-Higashi syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Chédiak-Higashi syndrome

NICE Guidance on Chédiak-Higashi syndrome

NHS PRODIGY Guidance

FDA on Chédiak-Higashi syndrome

CDC on Chédiak-Higashi syndrome

Books

Books on Chédiak-Higashi syndrome

News

Chédiak-Higashi syndrome in the news

Be alerted to news on Chédiak-Higashi syndrome

News trends on Chédiak-Higashi syndrome

Commentary

Blogs on Chédiak-Higashi syndrome

Definitions

Definitions of Chédiak-Higashi syndrome

Patient Resources / Community

Patient resources on Chédiak-Higashi syndrome

Discussion groups on Chédiak-Higashi syndrome

Patient Handouts on Chédiak-Higashi syndrome

Directions to Hospitals Treating Chédiak-Higashi syndrome

Risk calculators and risk factors for Chédiak-Higashi syndrome

Healthcare Provider Resources

Symptoms of Chédiak-Higashi syndrome

Causes & Risk Factors for Chédiak-Higashi syndrome

Diagnostic studies for Chédiak-Higashi syndrome

Treatment of Chédiak-Higashi syndrome

Continuing Medical Education (CME)

CME Programs on Chédiak-Higashi syndrome

International

Chédiak-Higashi syndrome en Espanol

Chédiak-Higashi syndrome en Francais

Business

Chédiak-Higashi syndrome in the Marketplace

Patents on Chédiak-Higashi syndrome

Experimental / Informatics

List of terms related to Chédiak-Higashi syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S; Raviteja Guddeti, M.B.B.S. [2]

For patient information on this page, click here

Synonyms and keywords: Oculocutaneous albinism with leukocyte defect; Beguez Cesar disease; Chediak-Steinbrinck-Higashi Syndrome; leukocytic anomaly albinism

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

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 arises from a microtubule polymerization defect which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy.

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.

Classification

Pathophysiology

Chediak-Higashi syndrome 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.

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.

Associated features:

  • Abnormalities in melanocytes (albinism)
  • Nerve defects
  • Bleeding disorders
  • Periodontal disease of deciduous dentition

Genetics

Chediak-Higashi syndrome is inherited in a autosomal recessive pattern.

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]

Differentiating Chédiak-Higashi syndrome from Other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Natural History

Complications

Prognosis

Death often occurs in the first 10 years of life, from chronic infections or accelerated disease that results in lymphoma-like illness. However, some affected children have survived longer.

Diagnosis

Diagnostic Criteria

History and Symptoms

Patients with Chediak-Higashi syndrome usually present with thefollowing symptoms:

Physical Examination

Skin

Eye

Abdomen

Neurologic

Laboratory Findings

  • Complete blood count and differential count - reveal neutropenia, thrombocytopenia
  • Hypergammaglobulinemia
  • Bleeding time - prolonged
  • Liver function tests - elevated bilirubin
  • Peripheral blood smear - giant granules in neutrophils, eosinophils, and granulocytes are seen when examined using light microscopy.
  • Bone marrow smear - peroxidase positive giant inclusion bodies in leukocyte precursor cells. The inclusion bodies contain lysosomal enzymes.
  • Fluorescence cytometric analysis of leukocyte granules

Imaging

CT

  • Brain and spinal cord atrophy

MRI

  • Brain and spinal cord atrophy

EMG

  • Delayed nerve conduction

EEG

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.

Medical therapy

Surgery

Prevention

Genetic counseling is recommended before becoming pregnant if you have a family history of Chediak-Higashi.

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.

Template:WH Template:WS