Chediak-Higashi syndrome

Definition:

An inherited disorder of the immune system that results in chronic infection, decreased pigment, neurological disease, and early death.

Causes, incidence, and risk factors:

Chediak-Higashi is inherited as an autosomal recessive disease. Mutations have been found in the CHS1 gene. The primary defect in this disease is in intracellular granules. For example, a granule that contains melanin is not made properly in skin giving the pigmentary differences in patients. A neutrophil granule defect (an abnormality in the granules found in certain types of white blood cells that are essential for killing some bacteria, fungi, and viruses) causes the immune problems.

This is one of a group of disorders called oculocutaneous albinism which means decreased pigment in the eye and skin. Children who have inherited the disorder have partial albinism when compared to family members. There may be a silvery sheen to their hair, light-colored eyes, jerky eye movements (nystagmus), and increased infections in their lungs, skin and mucus membranes.

More serious than the pigmentation problems are the effects of this disease on the immune and nervous systems of the body. Surviving adults develop unsteady gaits (ataxia) and nerve abnormalities in the limbs (peripheral neuropathy) causing motor and sensory changes and weakness. Infection with certain viruses such as Epstein-Barr virus (EBV) can cause a fatal illness resembling a blood cancer, lymphoma.

Symptoms:

jerky eye movements (nystagmus)
decreased vision
bright light bothers the eyes (photophobia, literally = fear of bright light)
albinism (these children have a lighter complexion than unaffected family members)
silvery sheen to hair which may be fair in color
frequent infections (skin, oral, respiratory)
mental retardation and decline may be present
tremor, abnormal walking gait, seizures, numbness
muscle weakness

Signs and tests:

blood smear that shows giant granules in the white blood cells that are positive with stains for peroxidases
giant granules are found in cells from biopsy of skin, muscle, nervous system as well as white blood cells
abnormally low blood platelet or white blood cell levels
physical examination may show enlarged spleen, liver or jaundice
genetic testing may show mutations in the CHS1 gene
EEG may show seizures
brain MRI or CT scan may show small brain due to atrophy
EMG or nerve conduction velocity testing may show delayed nerve conduction
red light reflex of the eye (frequently seen in albinism)
abnormal immune function tests

Treatment:

There is no specific treatment for Chediak-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.

Expectations (prognosis):

The frequent infections of Chediak-Higashi syndrome cannot be prevented. The terminal phase of the illness is not treatable.

Complications:

frequent infections especially with Epstein-Barr virus
a lymphoma-like cancer
early death

Calling your health care provider:

Call your health care provider if you have a family history of this disorder and you are planning to have children.

Call for an appointment with your health care provider if your child shows symptoms of Chediak-Higashi syndrome.

Prevention:

Genetic counseling is recommended for prospective parents with a family history of Chediak-Higashi. Intrauterine prenatal diagnosis is may be available for this disease.

Review Date: 11/12/2001
Reviewed By: David G. Brooks, M.D., Ph.D., Division of Medical Genetics, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network.

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