Danon Disease

What is Danon disease?

Danon disease is a rare genetic disorder that can affect you in many ways. It most often damages your heart, muscles, retina and brain, though symptoms vary from person to person.

Danon disease belongs to a group of more than 50 conditions known as lysosomal storage disorders (LSD). When you have a lysosomal storage disorder, your cells have trouble breaking down certain things, including food molecules and waste. This causes a buildup of harmful materials (toxins) that damage your cells and organs.

The condition is passed down in families (inherited). It typically passes from parents to children, though children who are assigned male at birth (AMAB) are more affected than children who are assigned female at birth (AFAB). 

What are symptoms of Danon disease?

Symptoms of Danon disease vary from person to person, but key features include:

• Heart disease (cardiomyopathy): These symptoms are usually the first to develop, and may include chest pain or tightness, fatigue and a sensation of fluttering or pounding in your chest.
• Muscle weakness (myopathy): You may have difficulty sitting or walking or experience weakness in your back, neck, shoulders and upper arms or upper thighs.
• Eye problems (retinopathy): You may have blurred vision, eye floaters or flashes.
• Intellectual disabilities: These are more common in people AMAB. They include behavioral problems, speech or language delays (common) and psychiatric issues (rare).

The impact of sex

In people AMAB, symptoms typically emerge in childhood or adolescence. They often progress rapidly and become severe. In people AFAB, symptoms may not develop at all or occur in late adolescence or young adulthood. Symptoms can progress slowly and are often mild but may become severe.

Types of cardiomyopathy

Danon disease typically involves one of two types of cardiomyopathy. They are:

• Hypertrophic cardiomyopathy (most common overall).
• Dilated cardiomyopathy (more common among those AFAB).

What causes Danon disease?

Danon disease occurs due to changes (mutations) in a specific gene called LAMP2. Researchers believe this genetic mutation leads to a problem in the wall (membrane) of the lysosome. But researchers don’t know the exact way this disorder occurs.

How is Danon disease diagnosed?

You or your healthcare provider may notice symptoms of Danon disease. Your provider will ask you about the symptoms and do several tests to confirm Danon disease and rule out other diseases.

Healthcare providers use a DNA test (genetic testing) to help diagnose Danon disease and rule out other conditions. Based on your symptoms, your provider may also recommend:

• Laboratory (blood) work.
• An eye exam.
• An ultrasound.
• A CT scan (computed tomography scan).
• An MRI (magnetic resonance imaging).
• A skeletal muscle biopsy.

Cardiac tests can assess how well your heart works. Tests may include:

• Heart biopsy (cardiac biopsy).
• Heart MRI.
• Electrocardiogram (EKG).

What conditions may resemble Danon disease?

Conditions with some similar symptoms include:

• Congenital glycogen storage disease (GSD) of the heart.
• Infantile autophagic vacuolar myopathy.
• Other cardiomyopathies, including sarcomeric hypertrophic cardiomyopathy or dilated cardiomyopathy.
• Pompe disease.
• Wolff-Parkinson-White (WPW) syndrome (may appear with Danon disease).
• X-linked myopathy with excessive autophagy.

What is the treatment for Danon disease?

Treatment for Danon disease depends on your symptoms and how severe they are. You’ll work together with your healthcare team to develop a treatment plan that’s right for you. This may include:

• Assistive devices, like eyeglasses or other vision aids, hearing aids, a walker or wheelchair.
• Psychotherapy (talk therapy) or speech therapy.
• Educational support for learning disabilities.
• Physical therapy to build muscle strength.

For heart issues, your specialist may recommend:

• Implantable cardioverter defibrillator (ICD) to treat symptoms of arrhythmia.
• Holter monitor to record your heart activity.
• Medication to ease problems with your heart, including cardiomyopathy.
• Procedures like ablation therapy to treat an irregular heart rhythm.

You may require a heart transplant if cardiomyopathy progresses rapidly. Early diagnosis and treatment are important to prevent life-threatening complications, like sudden cardiac death and early-onset heart failure.

Who might be on my treatment team for Danon disease?

Danon disease requires a team that should include a primary care provider (PCP) and several specialists. Your team may also include:

• Cardiologist (heart and blood vessel specialist).
• Eye care specialists.
• Geneticist (genetics expert).
• Neurologist (brain, spinal cord and nerves expert).
• Neuromuscular (muscle and nerve) expert.
• Ophthalmologist (eye care specialist).

Your care team monitors and adjusts medications or therapies based on your condition and any side effects you’re having.

Is there a cure for Danon disease?

Danon disease has no cure. But your provider can recommend treatments that help manage symptoms to optimize your health and quality of life.

How can I reduce my child’s risk of developing Danon disease?

Nothing you do can reduce your child’s risk of developing Danon disease. It happens because of a genetic change. If Danon disease runs in your family, talk to your healthcare provider about prenatal genetic testing.

What’s the outlook for Danon disease?

The outlook for Danon disease depends on several factors like what your symptoms are, how severe they are and how quickly the disease progresses. Your healthcare provider is the best person to talk to about what to expect in your specific case.

Danon disease life expectancy

On average, life expectancy for people with Danon disease is 19 for those AMAB and 34 for those AFAB. Many people require a heart transplant.

Your care team will work closely with you to manage your symptoms. They’ll also navigate you to helpful resources, so you and your family can get the support you need.

Who discovered Danon disease?

Moris Danon, MD, an American neurologist, first described the disease in 1981. He based his findings on two young patients with intellectual disabilities, enlarged hearts (cardiomegaly) and muscle weakness (proximal myopathy).

A note from Cleveland Clinic

Danon disease is a difficult and devastating diagnosis to receive. As you begin to navigate what it means to have this rare genetic condition, try to take it one day at a time. Surround yourself with support, from your care team to your friends and family. Since the disease is rare, you may find yourself doing a lot of teaching, even as you seek emotional support. And although it might be difficult to find other people or families who are in the same situation — even online — you might be able to cast a wider net. You might find support in groups for patients and families with other rare diseases or cardiomyopathies.

While Danon disease has no cure, your healthcare providers can recommend treatments to manage your symptoms. Your team will work closely with you so you can lead the fullest life possible.