Telomere Biology Disorders

What are telomeres?

Telomeres are sections of DNA found at the ends of chromosomes. They act as protective caps, helping to protect chromosomes from damage.

As we get older, telomeres become shorter. An enzyme, called telomerase, helps maintain and restore telomeres in certain cells, including the types of cells that need to divide frequently, such as bone marrow, skin, and the lining of the lungs and gut.

When the telomere becomes too short, cells may no longer divide properly and may stop functioning or die. In tissues that depend on regular cell renewal, this can impair the function of organs, and in severe cases, contribute to organ failure.

What are telomere biology disorders?

Telomere biology disorders are rare, genetic conditions that are caused by changes (mutations) in the genes responsible for maintaining telomeres. These mutations cause the telomeres to shorten too quickly, or they are abnormally short from birth. This causes cells to age or stop functioning earlier than they should.

Telomere biology disorders can affect many organs and systems in our bodies. The symptoms vary in different people and may develop in childhood or adulthood.

What causes telomere biology disorders?

Telomere biology disorders are caused by variations in our genes. These variations affect the body’s ability to maintain healthy telomeres.

Who is at risk of telomere biology disorders?

Telomere biology disorders are rare, but you may be at risk if:

• You have a family history of a telomere biology disorder.
• A family member has had pulmonary fibrosis, liver disease or bone marrow failure at a young age.
• You have a history of unexplained low blood cell counts.
• You or a family member has dyskeratosis congenita or another telomere biology disorder.

What are the symptoms of telomere biology disorders?

The symptoms of telomere biology disorders will vary depending on the tissues and organs that are affected.

Common signs of telomere biology disorders include:

• Bruising easily
• Chronic cough
• Fatigue
• Frequent infections
• Nail abnormalities
• Liver disease
• Low blood cell count
• Premature graying of the hair
• Shortness of breath
• Skin pigment changes
• Slow wound healing
• White patches inside the mouth

Which conditions are telomere biology disorders associated with?

Telomere biology disorders are linked to a number of conditions, including:

• Acute myeloid leukemia
• Aplastic anemia
• Bone marrow failure
• Certain immune deficiencies
• Dyskeratosis congenita
• Hepatopulmonary syndrome
• Interstitial lung disease
• Liver fibrosis and cirrhosis
• Myelodysplastic syndromes
• Pulmonary arteriovenous malformations
• Pulmonary fibrosis

How are telomere biology disorders diagnosed?

Diagnosing telomere biology disorders can be challenging because the symptoms are often similar to other medical conditions. Diagnosis usually involves:

• A physical exam
• Review of personal medical history and family history
• Genetic testing to try and identify gene variations that may cause disease
• Telomere length testing
• Bone marrow biopsy (if bone marrow failure is suspected)
• Pulmonary function testing
• Imaging tests, such as ultrasound of the liver or CT scan of the lungs

How are telomere biology disorders treated?

Treatment of telomere biology disorders focuses on managing symptoms, preserving organ function and preventing complications. Currently, there is no cure for telomere biology disorders.

Treatment may include:

• Ongoing monitoring by a team of specialists
• Genetic counseling
• Medications to manage lung or liver disease
• Medications, including growth factors or androgens, to help manage bone marrow failure in certain patients
• Antiviral or antibiotic medications to treat infections
• Blood transfusions if bone marrow failure is present
• Bone marrow transplant (stem cell transplantation) if bone marrow failure is severe
• Lung transplant or liver transplant in select patients with severe organ disease.

Can telomere biology disorders be prevented?

Telomere biology disorders are genetic disorders and cannot currently be prevented. Early diagnosis and specialist care of telomere biology disorders can ensure complications are identified sooner.

Once the condition has been diagnosed, people can take steps to avoid factors that may trigger or worsen the disease. For example, avoiding smoking may help prevent disease activation in some people.

For people with a family history of telomere biology disorders, genetic counseling can help you to understand your risk and discuss whether genetic testing may be appropriate.