Which are the causes of Chediak Higashi Syndrome?

Chediak-Higashi Syndrome (CHS) is a rare genetic disorder that affects various body systems, including the immune system, nervous system, and pigmentation. It is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the syndrome.

1. Genetic Mutation: The primary cause of Chediak-Higashi Syndrome is a mutation in the LYST gene, which provides instructions for producing a protein called lysosomal trafficking regulator (LYST). This protein plays a crucial role in the function of lysosomes, which are responsible for breaking down and recycling cellular waste materials. The mutation in the LYST gene leads to a dysfunctional LYST protein, impairing the normal functioning of lysosomes.

2. Impaired Lysosome Function: The malfunctioning lysosomes in individuals with CHS are unable to effectively break down waste materials within cells. As a result, these waste materials accumulate and form abnormal structures called giant cytoplasmic granules. These granules can be observed in various cells, including white blood cells, melanocytes (pigment-producing cells), and nerve cells.

3. Defective Immune System: The accumulation of giant cytoplasmic granules in white blood cells affects the normal functioning of the immune system. These cells, known as granulocytes, are responsible for defending the body against infections. In CHS, the impaired granulocytes are less effective in destroying bacteria and other pathogens, leading to an increased susceptibility to recurrent infections.

4. Albinism and Vision Problems: The malfunctioning melanocytes, which produce the pigment melanin responsible for hair, skin, and eye color, result in a reduced or absent pigmentation. This leads to a characteristic feature of CHS called partial albinism, where individuals have light-colored hair, fair skin, and light-colored irises. Additionally, the abnormal pigmentation in the eye can cause vision problems such as decreased visual acuity, nystagmus (involuntary eye movements), and photophobia (sensitivity to light).

5. Neurological Complications: The LYST gene mutation also affects the normal functioning of nerve cells. Individuals with CHS may experience various neurological complications, including intellectual disabilities, developmental delays, seizures, and problems with coordination and balance. These symptoms can vary in severity among affected individuals.

6. Hematological Abnormalities: CHS can also lead to abnormalities in blood clotting, resulting in prolonged bleeding and easy bruising. This is due to the impaired function of platelets, which are essential for blood clot formation.

7. Accelerated Lymphoproliferative Syndrome: Another significant complication of CHS is an increased risk of developing a condition called accelerated lymphoproliferative syndrome (ALPS). ALPS is characterized by the abnormal growth of lymphocytes, a type of white blood cell, leading to enlarged lymph nodes, spleen, and liver. This condition can further compromise the immune system and increase the risk of developing certain cancers.

Chediak-Higashi Syndrome is a complex disorder with various manifestations affecting multiple body systems. Early diagnosis and appropriate management are crucial in providing supportive care and minimizing complications associated with the syndrome.