Chédiak-Higashi syndrome

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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]

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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. ISBN 978-3-211-21396-4. doi:10.1007/978-3-211-69500-5_19. 
  2. "Chediak–Higashi syndrome". Retrieved 2008-11-06. 



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