Chediak-Higashi syndrome

Synonyms

6

Overview

Chediak-Higashi syndrome (CHS)  is a condition that affects many parts of the body, particularly the immune system. This disease damages immune system cells, leaving them less able to fight off invaders such as viruses and bacteria. As a result, most people with Chediak-Higashi syndrome have repeated and persistent infections starting in infancy or early childhood. These infections tend to be very serious or life-threatening.

Chediak-Higashi syndrome is also characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and light-colored hair, often with a metallic sheen. Oculocutaneous albinism also causes vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).

Many people with Chediak-Higashi syndrome have problems with blood clotting (coagulation) that lead to easy bruising and abnormal bleeding. In adulthood, Chediak-Higashi syndrome can also affect the nervous system, causing weakness, clumsiness, difficulty with walking, and seizures.

If the disease is not successfully treated, most children with Chediak-Higashi syndrome reach a stage of the disorder known as the accelerated phase. This severe phase of the disease is thought to be triggered by a viral infection. In the accelerated phase, white blood cells (which normally help fight infection) 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.

A small percentage of people with Chediak-Higashi syndrome have a milder form of the condition that appears later in life. People with the adult form of the disorder have less noticeable changes in pigmentation and are less likely to have recurrent, severe infections. They do, however, have a significant risk of progressive neurological problems such as tremors, difficulty with movement and balance (ataxia), reduced sensation and weakness in the arms and legs (peripheral neuropathy), and a decline in intellectual functioning.

Symptoms

  • Sensitivity to light
  • Shifting nystagmus upon exposure to light
  • Weakness
  • Fever
  • Cerebellar tremor
  • Weakened immune system
  • Repeated and persistent infections beginning in infancy and childhood
  • Oculocutaneous albinism
  • Blood clotting problems
  • Nervous system abnormalities (e.g., weakness, difficulty walking, and seizures)
  • Abnormality of neutrophils
  • Abnormality of temperature regulation
  • Anemia
  • Bruising susceptibility
  • Cognitive impairment
  • Generalized hypopigmentation
  • Gingival bleeding
  • Hepatomegaly
  • Hypopigmentation of hair
  • Lymphadenopathy
  • Ocular albinism
  • Paresthesia
  • Periodontitis
  • Recurrent cutaneous abscess formation
  • Recurrent respiratory infections
  • Skin ulcer
  • Splenomegaly
  • Thrombocytopenia

Causes

Mutations in the CHS1 gene (also called LYST) have been found to be connected with Chédiak–Higashi Syndrome. 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 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.

Prevention

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

Diagnosis

A complete diagnostic work-up for albinism includes a:

  • Physical exam
  • Description of changes in pigmentation
  • Thorough exam of the eyes
  • Comparison of your child's pigmentation to that of other family members

 

A medical doctor specializing in vision and eye disorders (ophthalmologist) should conduct your child's eye exam. The exam will include an assessment of potential nystagmus, strabismus and photophobia. The doctor will also use a device to visually inspect the retina and determine if there are signs of abnormal development. A simple test can measure the brain waves produced when light or a reversing pattern is flashed into each eye. This can indicate the presence of misrouted optical nerves. If your child has only one eye impairment, such as nystagmus, another condition may be the cause. Disorders other than albinism can affect skin pigmentation, but these don't cause all of the visual problems associated with albinism.

The diagnosis of CHS is usually made by the presence of 'giant granules' in microscopic analysis of white blood cells. 'Giant inclusion bodies' can also be seen in the cells that develop into white blood cells (leukocyte precursor cells) in the bone marrow.

Pigment clumping in hair that can be seen under light microscopy is another method for diagnosis that would be done if a blood smear showed enlarged granules.

CHS can be diagnosed in an unborn child (prenatally) by examining a sample of hair from a fetal scalp biopsy or testing white blood cells (leukocytes) from a fetal blood sample.

Prognosis

Death often occurs in the first 10 years of life because of chronic infections or accelerated disease that results in lymphoma-like illness. However, persons have survived for longer.

Treatment

There is no specific treatment for Chediak-Higashi syndrome. Bone marrow transplants appear to have been successful in several patients. Bone marrow transplant corrects the immune and bleeding abnormalities and prevents the development of the accelerated phase. If the accelerated phase occurs, hemophagocytosis must be in remission before a bone marrow transplant can occur. Those patients are given chemotherapy to get the accelerated phase into remission. Bone marrow transplant can occur after the patient is in remission. Before major procedures, a drug to prevent excessive bleeding, DDVAP, can be administered.

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. Platelet transfusions may be necessary if bleeding becomes excessive after injury or surgery.

People with CHS should minimize unprotected sun exposure. When affected individuals are exposed to sunlight, sunglasses and sunscreens applied to the skin can be helpful. Genetic counseling may be of benefit for people with CHS and their families.