Chédiak-Higashi syndrome: what is it, causes, symptoms, treatment, prognosis

What is Chédiak-Higashi Syndrome?

Chédiak-Higashi syndrome (abbr. SCH) is a rare, hereditary, complex, immune disease that usually occurs in childhood, characterized by a decrease in pigmentation of the skin and eyes (oculocutaneous albinism), immunodeficiency with increased susceptibility to infections, a tendency to bruises and easy bleeding. Neurological disorders are also common. SCH is transmitted as an autosomal recessive genetic disease.

Signs and symptoms

Symptoms of Chédiak-Higashi syndrome may be evident already in early childhood. Hair is usually light or light brown with a silvery tinge. Sick children may be abnormally sensitive to light (photosensitivity) due to a decrease in pigment in the eyes and skin, and may exhibit rapid involuntary eye movements (nystagmus). More important and more serious is the effect of SCH on the patient's immune and nervous systems.

On SCH, leukocytes (white blood cells) contain abnormal granules that are markedly enlarged. These granules can be seen by looking at blood cells under a microscope. These abnormal granules interfere with the ability of white blood cells to fight infection. Children are prone to frequent bacterial, viral and fungal infections, especially of the skin and respiratory tract. Children with MFS may also have abnormally low white blood cell counts.

Children with this condition can easily get bruised and bruised or bleed excessively even with minor injuries. Platelet counts in patients are usually normal but not functioning properly, causing easy bruising or prolonged bleeding.

The disease can be divided into classic and atypical (mild) forms. People with the atypical form may be less susceptible to serious infections and have milder symptoms. Children with the classic form of the disease are at risk of developing an accelerated phase. The accelerated phase occurs in 85% of patients and can occur at any age. The accelerated phase is caused by the overproduction of lymphocytes by the immune system. Patients may develop symptoms such as:

• fever (high temperature);
• inflammation of the lymph nodes;
• enlarged liver;
• enlargement of the spleen;
• anemia;
• low level of leukocytes in the blood;
• low level of platelets in the blood.

It is a serious condition and requires immediate treatment.

Neurological symptoms begin in early adulthood. Symptoms affecting the nervous system include:

• unstable posture and walking (ataxia);
• loss of sensation in the arms and legs (peripheral neuropathy).

This can lead to physical weakness and disability. Some patients may have symptoms that resemble Parkinson's disease.

SCH reasons

Chédiak-Higashi syndrome is inherited as an autosomal recessive genetic trait. The responsible gene is mapped to chromosomal locus 1q42.1-Q42.2 and is known as the gene Lyst.

An abnormal gene affects the "patterns" or movement of proteins in cells. Proteins (or enzymes) that are meant to move from one part of the cell to another may be misdirected or not transported.

For example, the granule in which the skin pigment (melanin) is formed is interfered with so that the pigment cannot be transferred to the corresponding skin cell. Likewise, a defect in transport in leukocytes renders the cell helpless in killing infectious agents such as viruses or bacteria and causes immune problems.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information of each person. The cells of the human body usually have 46 chromosomes. Pairs of human chromosomes are numbered 1 through 22, and the sex chromosomes are labeled X and Y. Men have one X and one Y chromosome, while women have two X chromosomes. Each chromosome has a short arm, labeled "p", and a long arm, labeled "q". Chromosomes are further subdivided into many numbered bands. For example, "chromosome 1q42.1" refers to band 42.1 on the long arm of chromosome 1. The numbered stripes indicate the location of the thousands of genes present on each chromosome.

Genetic diseases are defined by a combination of genes for a specific trait that are found on chromosomes received from the father and mother.

Recessive genetic disorders occur when a person inherits an abnormal gene for one trait from each parent. If a person receives one normal gene and one abnormal gene for a disease, the person will be a carrier of the disease, but usually asymptomatic. The risk that both carrier parents pass on the defective gene and therefore have a sick child is 25% with each pregnancy. The risk of having a carrier child, like the parents, is 50% with each pregnancy. The probability of a child receiving normal genes from both parents and being genetically normal for a given trait is 25%. The risk is the same for men and women.

All humans carry 4-5 abnormal genes. Parents who are close relatives (i.e. from the same family, for example, a brother and sister) are more likely to have a sick child than parents from different families.

Affected populations

Chédiak-Higashi syndrome is a very rare condition that affects men and women in equal numbers. Often appears at birth or shortly after. There does not appear to be a higher risk for any particular ethnic or racial group. Fewer than 500 cases have been reported. In 85% of patients, the syndrome progresses to an accelerated phase.

SCH diagnostics

The diagnosis of SCH is usually made by the presence of "giant granules" on microscopic analysis of leukocytes. "Giant inclusion bodies" can also be seen in cells that turn into white blood cells (white blood cell precursors) in the bone marrow.

Clumping of pigment in hair, which can be seen with light microscopy, is another diagnostic method that is performed if enlarged granules are found in a blood smear.

Symptomatic Disorders

Symptoms of the following disorders may be similar to those of Chédiak-Higashi syndrome. Comparisons can be useful for differential diagnosis:

• Griszelli Syndrome - a rare hereditary disease characterized by partial albinism and abnormalities of platelets and leukocytes. Symptoms are similar to those of SCH. There are 3 different types of Griszelli syndrome. Type 2 is very similar to SCH in that patients have pigment and immune disorders. Patients are also at risk of an accelerated phase. On laboratory analysis, white blood cells do not have giant granules like those seen in Chédiak-Higashi syndrome; Thus, diagnoses are made differently based on these granules.
• Germanic-Pudlak Syndrome - a rare hereditary disease characterized by a decrease in pigmentation of the skin, hair and / or eyes (albinism), abnormal platelets and excessive accumulation of fatty substances (ceroids) in various parts of the body. Symptoms of Germanicus-Pudlack syndrome include discoloration of the skin, hair, and eyes, blurred vision, and excessive bleeding. Ceroid fatty deposits in the lungs, intestines, heart and / or kidneys can cause dysfunction in many organs of the body. One type of Germanicus-Pudlack syndrome can also have immune disorders. Often the first symptoms of the syndrome in a child are easy bruising, bleeding gums, nosebleeds, and excessive bleeding after surgery or injury.
• Oculocutaneous albinism - a disease that leads to visual impairment and depigmentation of the iris / retina. Depigmentation can range from mild to complete. Oculocutaneous albinism can be differentiated from SCH by the absence of an infectious history or neurologic abnormality.
• Familial hemophagocytic lymphohistiocytosis characterized by highly active macrophages and T-lymphocytes, which act as acute diseases with fever, decreased blood cell count, enlargement of the spleen and liver. The age of onset of the disease varies. Neurological symptoms can also manifest as pressure in the brain, irritability, neck stiffness, low muscle tone, spastic muscles, epilepsy, cranial nerve palsy, loss of muscle control (ataxia), hemi / quadriplegia, blindness and coma. Liver dysfunction and destruction of immune cells are also symptoms. Median infant survival is less than two months, usually due to infection. The disease is autosomal recessive and is caused by a mutation in one of the FHL1-FHL5 genes.

Treatment

Treatment for Chédiak-Higashi syndrome varies depending on the stage of the disease at the time of diagnosis. Ideally, a bone marrow transplant should be performed before the patient develops an accelerated phase. Bone marrow transplantation eliminates immune disorders and bleeding and prevents the development of the accelerated phase. If an accelerated phase occurs, the hemophagocytosis must be in remission before a bone marrow transplant is performed. These patients are given chemotherapy to get an accelerated phase in remission. A bone marrow transplant can be performed after the patient is in remission. Before major procedures, you can use a drug to prevent excessive bleeding, Desmopressin.

Apart from these options, treatment for SCH is symptomatic. If bacterial or fungal infections occur, they should be treated promptly with antibiotics or antifungal medications. Acute viral infections can be treated with antiviral drugs. A platelet transfusion may be necessary if bleeding becomes excessive after injury or surgery.

People with Chédiak-Higashi syndrome should minimize exposure to the sun. When sufferers are exposed to sunlight, sunglasses and sunscreen applied to the skin can be helpful.

Forecast

Chédiak-Higashi syndrome usually results in early death from infection or, less commonly, bleeding. Unresolved respiratory and skin infections are usually fatal before the child with MFS reaches 10 years of age. Longer survival is possible, but lymph nodes, spleen, and liver enlarge and malignant lymphoma develops. However, there are patients who have lived to be 20 years old.