Danon Disease

Danon disease is a rare inherited disease caused by a change in the LAMP2 gene. This gene makes a protein that is important for lysosomes, the parts of the cell that recycle damaged cell components through a process called autophagy. When this protein does not work, waste material builds up in small bubbles (vacuoles) inside cells, especially in the heart muscle and skeletal muscles. This disease belongs to the group of storage diseases that can look like hypertrophic cardiomyopathy, and it is covered together with similar causes on the Infiltrative Cardiomyopathy page.

Different in Males and Females

The LAMP2 gene is located on the X chromosome. Males have only one X chromosome, so symptoms usually appear earlier, often in childhood or the teenage years, and are more severe. In males, the heart muscle usually thickens markedly, and many need a heart transplant before age 30. Females have two X chromosomes, so symptoms usually appear later, often in young adulthood, and the form of the disease varies more, including a heart muscle that weakens and enlarges. Even so, females can also have severe disease.

More Than Just the Heart

Besides the heart, Danon disease can affect the skeletal muscles, making the shoulder and thigh muscles feel weak; the retina of the eye, affecting vision; and, in some males, learning ability. In females, muscle and eye involvement is usually milder. An ECG often shows a pre-excitation pattern, an extra electrical pathway like in Wolff-Parkinson-White syndrome, covered on the Wolff-Parkinson-White Syndrome page. Blood tests can show raised levels of the muscle enzyme creatine kinase and of liver enzymes.

Why Diagnosis Matters

Danon disease is often mistaken for ordinary hypertrophic cardiomyopathy, even though it progresses faster. The diagnosis is confirmed with genetic testing, covered on the LAMP2 Genetic Test page. An accurate diagnosis helps your doctor plan rhythm monitoring, the timing of ICD placement, transplant referral, and testing of family members. When one family member is diagnosed, family testing can find other carriers before symptoms appear, so monitoring can start earlier. Gene therapy for Danon disease is being studied in clinical trials, but it is not yet routine treatment.

Suspicion arises when heart muscle thickening is found in a child, teenager, or young adult, especially with a pre-excitation pattern on the ECG, muscle weakness, raised creatine kinase, vision problems, or learning difficulties. The 2023 ESC guidelines describe these signs as clues to look for causes other than the heart muscle protein abnormalities usually found in hypertrophic cardiomyopathy.

Echocardiography and cardiac MRI assess thickness, scar tissue, and pumping strength. The diagnosis is confirmed with LAMP2 genetic testing. If a gene variant is found, genetic counseling and family testing, including the mother and sisters who may be carriers, can be done in a more targeted way. An eye examination by an ophthalmologist and a developmental assessment in children complete the evaluation.

Go to the emergency room right away if fainting occurs, or if you have a very fast heartbeat with dizziness or severe shortness of breath. Make an appointment with a cardiologist if:

• Your child or teenager has been found to have a thick heart muscle, especially with muscle weakness or learning difficulties
• An ECG shows a pre-excitation or Wolff-Parkinson-White pattern together with heart thickening
• A family member has been diagnosed with Danon disease or has had cardiomyopathy, a heart transplant, or sudden death at a young age
• You are a female carrier of a LAMP2 variant and have not had a heart checkup
• A person with Danon disease starts getting short of breath or tired more quickly