Introduction

Chediak-Higashi Syndrome (CHS) is a rare condition caused by changes in the LYST gene, leading to immune dysfunction and defects in lysosomal trafficking. Patients often present with oculocutaneous albinism, bleeding problems, and recurrent infections. Without treatment, most affected individuals progress to the accelerated phase, a severe, often virus-triggered stage characterised by uncontrolled proliferation of white blood cells that infiltrate multiple organs. 

This article helps you understand Chediak-Higashi syndrome by focusing on two major clinical features—hepatosplenomegaly (enlargement of the liver and spleen) and lymphadenopathy (enlarged lymph nodes)—examining their underlying causes, symptoms, and significance in disease progression.

Chediak-Higashi Syndrome

Let’s start with the name Chediak-Higashi; it refers to a French physician (Moises Chediak) and a Japanese physician (Ototaka Higashi), who were involved in the consultation of the initial family with atypical characteristics, presenting with a novel disease. Chediak-Higashi Syndrome is a very uncommon condition, inherited from parents to a child in an autosomal recessive pattern.

To break that down, this means that the genetic change occurs in one of the numbered 22 chromosomes as opposed to the sex chromosomes (the autosomal part); and an individual must have inherited the altered, faulty copy from both of their parents to be affected by the syndrome, meaning both of their parents are carriers (the recessive part). 

Chediak-Higashi syndrome affects various body parts; however, it predominantly affects the immune system. This means that affected individuals often suffer from persistent infections, which are more likely to become life-threatening.

So, what causes it?

A change in the LYST gene, which tells our cells to make a protein called the ‘lysosomal trafficking regulator’, affects the person. This protein helps to transport various materials from within the cell to lysosomes (which can be thought of as recycling centres within cells) to be broken down. When this trafficking protein becomes disrupted by a mutation in the LYST gene, lysosomal size and structure can be affected.

A good example of this is the enlargement of lysosomes of the immune system, meaning immune system cells can’t properly respond to invaders like bacteria. The bacteria that enter the cell can’t be properly taken to the ‘recycling centre’, resulting in recurrent, severe infections.

Characteristics of individuals with Chediak-Higashi syndrome

Individuals with Chediak-Higashi syndrome are often characterised by lighter skin, eye and hair colour, known as oculocutaneous albinism. In addition, oculocutaneous albinism can present as vision-related issues, including reduced sharpness and increased sensitivity to light. These changes occur due to the changes in melanosomes, tiny structures within special skin cells called melanocyte cells, which are related to lysosomes. 

The pigment melanin is formed inside melanosomes. Melanosomes are unusually larger in individuals with Chediak-Higashi syndrome, trapping melanin inside them, leading to those lighter features. 

Furthermore, affected individuals commonly experience blood-clotting (coagulation) issues. Blood clotting is important when you get an injury to create a temporary plug using elements called platelets and clotting factors. Clotting issues mean the person may bruise more easily and bleed abnormally. Upon reaching adulthood, affected individuals with Chediak-Higashi syndrome may experience weakness, difficulty walking, clumsiness and seizures due to their affected nervous system.¹

The accelerated phase

If Chediak-Higashi syndrome is not properly treated, many people eventually reach a more severe stage called the accelerated phase, thought to be triggered by viral infection. In this phase, white blood cells divide too quickly, and the person’s body is unable to control the rate at which this happens. These masses of white blood cells then invade organs throughout the body. While white blood cells are usually the soldiers that help us to fight infections, we don’t want them to invade all of our organs. This phase may involve overwhelming infections and organ failure.

Hepatosplenomegaly

Spleno means spleen…

The spleen is a fist-sized organ located just below your left rib cage, it has a few important jobs such as filtering out old and damaged blood cells, producing white blood cells (soldiers!) to reduce the chances of getting an infection, and storing red blood cells and platelets (the other types of cells found in the blood) to help with the clotting of blood. 

Splenomegaly, the medical term for an enlarged spleen, is usually identified by a doctor during a physical exam because a healthy spleen is too small to feel. A healthy, normal spleen is up to 12 cm long and 70 grams in mass, while an enlarged spleen may be up to 20 cm long and up to 1000 grams in mass.

An individual with an enlarged spleen may experience symptoms such as pain/ fullness in the left upper stomach, which can spread to the left shoulder; feeling full after eating a small quantity or not eating at all due to the pressure from the enlarged spleen on the stomach; anaemia; frequent infections; and increased bleeding.

An enlarged spleen means there are fewer red blood cells around. This increases the frequency of infections and increased bleeding. There is also the risk of an enlarged spleen rupturing, leading to potentially life-threatening internal bleeding. Doctors suggest that individuals with an enlarged spleen avoid high-contact sports to reduce the risk of rupture.^2,3

Hepato means liver…

The liver is a large, football-shaped organ located in the upper right section of the abdomen. The key roles of the liver include filtering the blood to remove toxins, producing bile to help digest fats, making proteins that help in blood clotting, and regulating cholesterol within the body. 

Hepatomegaly is the term that describes an enlarged liver. An enlargement of the liver can cause an individual to experience symptoms such as fatigue, nausea and vomiting, yellowing of the skin and whites of the eyes and abdominal pain. If there is enough healthy tissue left, the liver may be able to repair itself.

For the best chance of recovery, individuals should manage their alcohol intake and take care to manage blood pressure, sugar and cholesterol.^4,5 

Put that together: Hepatosplenomegaly 

Hepatosplenomegaly is the enlargement of the spleen and the liver at the same time- ouch! That has got to be putting pressure on the other organs. 

When it is identified that a person has both an enlarged spleen and liver, this helps doctors to decide that an underlying disease is causing the enlargement rather than more localised causes for an enlargement of just one or the other. It is not only in Chediak-Higashi syndrome that the spleen and liver simultaneously become enlarged; both organs have big parts to play in blood filtering and the immune system, so cancers like leukaemia and lymphoma can cause the same problem. 

The spleen and the liver are connected through a shared blood flow channel, called the portal venous system. The portal venous system is a network of blood vessels that connects the digestive organs (such as the intestines, stomach, pancreas, and spleen) with each other. When blood leaves these digestive organs, it is directed to the liver via the portal vein instead of returning straight to the heart. This is so that the liver can check the blood and process any nutrients, toxins and waste products. An increase in blood pressure (known as hypertension) within this system is likely to cause hepatosplenomegaly because it is shared with both the spleen and the liver.

Lymphadenopathy

Lymphadenopathy, also known as swollen lymph nodes. Lymph node swelling is a natural reaction to illness or infection, but it can be uncomfortable, often feeling tender and painful in the sides of the neck.

Lymph nodes are part of the lymphatic system, a system that prevents infection and maintains fluid levels in the body. While it is uncomfortable, the swollen lymph nodes are actually good because they mean the body is working to get rid of an infection. They act as a filter to help get rid of any bacteria, cells or other nasties within the lymph fluid.

At the sides of the neck, swollen lymph nodes are the most common; however, one can develop the same under the armpits. When this happens, the medical terminology used is axillary lymphadenopathy. We have a huge network of lymph nodes throughout our body- about 600 of them!^6,7

Hopefully, you remember from earlier that in Chediak-Higashi syndrome, the lysosomes within immune cells are abnormal, leading to frequent and severe infections, and also this lymph node swelling. During the accelerated phase, one of the key places that those extra white blood cells head to is the lymph nodes, causing lymphadenopathy.

Summary

Chediak-Higashi Syndrome (CHS) is a rare condition caused by changes in the LYST gene, leading to immune dysfunction and defects in lysosomal trafficking. This distorts the recycling mechanism of the affected cells, which eventually affects the immune system. Patients often present with oculocutaneous albinism, bleeding problems, and recurrent infections. 

A more severe stage of Chediak-Higashi syndrome, called the accelerated phase. In which white blood cells divide too quickly, and invade organs throughout the body. While white blood cells are usually the soldiers that help us to fight infections, we don’t want them to invade all of our organs. This phase involves overwhelming infections and organ failure.

Hepatosplenomegaly is the enlargement of the spleen and liver simultaneously, which puts pressure on the other organs. It causes many other complications related to the intestine, spleen, and stomach.

Lymphadenopathy or lymph node swelling is a natural reaction to illness or infection, but it can be uncomfortable, often feeling tender and painful on the sides of the neck.