Chediak-Higashi syndrome (CHS)

Chediak-Higashi syndrome (CHS) is a rare condition that affects many parts of the body, most of all the immune system. Immune cells cannot fight germs well, so infections are common and can be serious. Many people also have light skin, hair and eyes (partial albinism), and they bruise and bleed easily.

A hallmark of CHS is very large granules, or packets, inside white blood cells. Doctors can see them when they look at a blood sample under a microscope. CHS is not a cancer, and it is not contagious.

CHS ranges from severe to mild. In the classic form, problems start in infancy or early childhood. In a milder (atypical) form, signs may not be noticed until the teen or adult years. Nearly everyone with CHS, whatever the form, develops nerve problems later in life.

CHS is caused by changes in both copies of a gene called LYST. This gene helps control lysosomes. These are small sacs inside cells that break down waste and germs. When LYST does not work, lysosomes and similar sacs grow too large and do not work properly.

This problem shows up in many kinds of cells. Killer immune cells (cytotoxic T cells and natural killer cells) cannot release what they need to destroy infected cells. Pigment cells trap their color inside, which causes the light coloring. Platelets lack some of the granules they need for clotting, which causes bleeding. Problems in nerve cells are thought to cause the nerve symptoms.

The pattern is autosomal recessive. Each parent usually carries one changed copy and is healthy. When both parents are carriers, each child has a 1 in 4 chance of having CHS.

Babies and young children with classic CHS often have repeated bacterial infections, mostly of the skin and lungs. Their hair is often light or silvery with a metallic shine. Eye problems include poor vision, fast eye movements they cannot control (nystagmus) and sensitivity to light. Platelet counts are usually normal, but the platelets do not work well. Easy bruising and bleeding from the gums or nose (mucosal bleeding) are common.

The most serious problem is called the accelerated phase. This is HLH (hemophagocytic lymphohistiocytosis), a runaway inflammation in which immune cells fill organs such as the liver, spleen and bone marrow. It causes fever, swollen glands, a large liver and spleen, and low blood counts. A viral infection, such as Epstein-Barr virus, is thought to set it off. A 2014 review says HLH develops in 50 to 85 percent of people with CHS, and it is fatal if not treated.

Nerve problems usually build slowly. Children may have learning difficulties or attention problems (ADHD). From the late teens or twenties, many people develop weakness and numbness in the feet and legs (neuropathy). Poor balance (ataxia), tremor and symptoms like Parkinson’s disease can also develop. Thinking and memory can decline over time.

CHS is often suspected in a child with light skin, silvery hair and repeated infections, or in a child who becomes very ill with HLH. A blood smear is a key test. Under the microscope, white blood cells in CHS contain giant granules, a finding doctors treat as a sure sign of the condition. Looking at a hair under a light microscope can also show clumps of pigment.

Other tests look at how the immune system works. The number and killing ability of natural killer cells may be low, and neutrophil counts may be low too. If HLH is suspected, doctors check blood counts, ferritin and other markers. They use the HLH-2004 criteria, which need 5 of 8 findings or a known gene cause. A spinal tap (lumbar puncture) and brain MRI can show whether HLH has reached the brain.

Genetic testing confirms CHS by finding changes in both copies of LYST. Once a family’s changes are known, brothers and sisters can be tested. Testing during a pregnancy, or of embryos before pregnancy (preimplantation testing), also becomes possible. In rare cases of the milder form, the diagnosis is made only in adulthood, when a blood smear is done because of nerve problems.

When HLH starts, the first goal is to calm it. Teams treat it the same way as familial HLH, with a steroid called dexamethasone and the chemotherapy medicine etoposide. Medicine may also be given into the spinal fluid if HLH reaches the brain. Infections are treated quickly.

In the United States, emapalumab (Gamifant) is approved for primary (inherited) HLH that does not respond, comes back or gets worse. It is also approved when standard treatment cannot be tolerated. In the European Union, approval for children was refused in January 2021, so access differs by country. None of these medicines corrects CHS. They are a bridge to transplant.

A donor stem cell transplant replaces the faulty blood-forming and immune system with a healthy one. It is the only treatment that corrects the immune and bleeding problems, and it keeps HLH from coming back. Results are best when transplant happens before HLH starts, or after HLH has been brought under control. Older, stronger chemotherapy before transplant was linked to more deaths. Centers have since moved toward gentler (reduced-intensity or reduced-toxicity) approaches.

Transplant does not fix everything. It does not change skin, hair or eye color, and it does not prevent the nerve problems that appear later. A 2014 review reports that people with the milder form do not benefit from transplant. Other care includes quick treatment of infections, sun protection and glasses. Care teams usually advise avoiding live vaccines and pain medicines such as aspirin and ibuprofen (NSAIDs), which can make bleeding worse.

For many families, the diagnosis comes when a baby with light or silvery hair has infection after infection, or becomes very sick with HLH. Sometimes the giant granules are first noticed on a blood test done for another reason. If HLH is active, treatment starts in the hospital and can last weeks to months, with blood tests, transfusions and steps to prevent infection. A donor search often starts at the same time.

Transplant brings months of hospital and clinic care. Afterward, teams watch for infection, graft-versus-host disease and the share of donor cells in the blood. Some children keep a mix of donor cells and their own cells and still stay free of infections and HLH. Follow-up continues into adulthood, because nerve problems can appear 20 years after a successful transplant.

Nerve and learning problems shape daily life for many people with CHS. Physical therapy and mobility aids help as weakness and balance problems progress. Some people with Parkinson-like symptoms are helped by a medicine called levodopa. School support, vision services and genetic counseling for the family are also part of care. Brothers and sisters are usually checked as early as possible, because finding CHS before HLH starts may allow a transplant before HLH.

A child with CHS who goes to transplant needs blood-forming cells from another person, because the child’s own cells carry the LYST changes. A healthy brother or sister who is a full tissue (HLA) match may be chosen. Each full sibling has a 1 in 4 chance of being a full match. Siblings are also checked for CHS itself, because a young sibling may have it before there are clear signs.

Many children have no matched family donor. In a registry study of 35 children with CHS, about a third received cells from an unrelated donor. The authors wrote that an unrelated donor may be a suitable choice when there is no matched sibling. Cord blood and half-matched (haploidentical) family donors have also been used. European recommendations from 2025 call primary HLH, whatever the gene behind it, a clear reason for a donor transplant, including with these other donors.

Timing matters. Transplant works best before HLH or once it is under control, so teams often begin a donor search soon after diagnosis. Joining a registry cannot promise a match for any one child. It adds to the pool that transplant teams search when a child needs a donor.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Without a transplant, classic CHS is often fatal in the first ten years of life, from infection or HLH. Transplant has changed this for many children. Results are best when transplant is done before HLH starts or after HLH is under control. In a registry study, children who still had active HLH at transplant did much worse.

Over the long term, the nervous system shapes the outlook. Transplant fixes the immune and bleeding problems, but nerve problems still develop in nearly everyone with CHS, including after a successful transplant. A 2024 review describes slowly worsening weakness, balance and thinking problems that start in the late teens or early adulthood. Within 10 years of these problems starting, many people need a wheelchair. In advanced disease, many people need full-time care, and serious infections often shorten life.

These figures come from small groups of children, many transplanted decades ago with harsher treatments than centers use now. They cannot predict how any one child will do.