Chediak-Higashi syndrome

Chediak-Higashi syndrome is a rare, inherited disorder that impairs the immune system and causes oculocutaneous albinism, leading to severe, recurrent infections and vision problems.

Overview

Chediak-Higashi syndrome damages immune system cells, making them less effective at fighting viruses and bacteria. Most affected individuals experience serious, life-threatening infections starting in infancy. The condition also affects pigmentation and, in later stages, the nervous system.

Symptoms

• Immune System: Repeated, persistent, and severe infections.
• Oculocutaneous Albinism: Abnormally light skin, hair, and eyes. Hair often has a metallic sheen.
• Vision Problems: Reduced sharpness, rapid involuntary eye movements (nystagmus), and sensitivity to light (photophobia).
• Bleeding Issues: Problems with coagulation leading to easy bruising and abnormal bleeding.
• Neurological Issues: In adulthood, patients may experience weakness, clumsiness, difficulty walking, seizures, tremors, and peripheral neuropathy.

The Accelerated Phase

If untreated, most children enter an "accelerated phase," often triggered by a viral infection. During this phase, white blood cells divide uncontrollably and invade organs, leading to fever, organ failure, and severe bleeding, which are typically life-threatening.

Causes

The syndrome is caused by mutations in the LYST gene, which provides instructions for the lysosomal trafficking regulator protein. This protein is essential for the transport of materials into lysosomes—the cell's "recycling centers."

• Mutations cause lysosomes to become abnormally large, interfering with cell function.
• In immune cells, these giant lysosomes prevent the cells from responding to bacteria.
• In pigment cells (melanocytes), melanin is trapped within giant melanosomes, preventing normal pigmentation.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the LYST gene in each cell must have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show symptoms.