Chédiak-Higashi syndrome
| Chédiak-Higashi syndrome | |
| ICD-10 | E70.3 (E70.340 ILDS) |
|---|---|
| ICD-9 | 288.2 |
| OMIM | 214500 |
| DiseasesDB | 2351 |
| MeSH | D002609 |
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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
Synonyms and keywords: Oculocutaneous albinism with leukocyte defect; Beguez Cesar disease
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.
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.
Associated features:
- Abnormalities in melanocytes (albinism)
- Nerve defects
- Bleeding disorders.
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]
Natural History, Complications and Prognosis
Complications
- Life threatening infections
- Pyodermas and deep abscesses
- Neuropathy
- Lifethreatening bleeding
- Loss of vision
- Renal failure
Diagnosis
History and Symptoms
Patients with Chediak-Higashi syndrome usually present with thefollowing symptoms:
- Dizziness
- Weakness
- Photophobia
- Tremor
- Photosensitive skin
- Neuropathy
- Frequent infections
- Numbness
- Seizures
- Unsteady walking (ataxia)
- Nosebleeds or easy bruising
- Intellectual disability (mental retardation)
Physical Examination
Skin
- Hypopigmentation skin - (albinism)
- Silvery hair
Eye
Abdomen
Neurologic
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
- Griscelli syndrome (also known as "Chédiak-Higashi like syndrome")
References
- ↑ 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.
- ↑ "Chediak–Higashi syndrome". Retrieved 2008-11-06.