Danon Disease is a rare, genetic condition characterized by a mutation or deletion of the LAMP2 (short for lysosome-associated membrane protein) gene located on the X chromosome. It can be either inherited from a parent with the condition or a new genetic change (‘de novo’). Danon Disease was first described almost 30 years ago. While over 160 mutations have been identified in the LAMP2 gene, Danon Disease is still not well understood and more research is needed to improve both diagnosis and treatment.
Danon Disease is a lysosomal storage disorder. Individuals with Danon Disease are missing the DNA instructions needed for the body to make the LAMP2 protein, which plays a role in lysosome function and the cell’s recycling system (known as autophagy). Lysosomes are compartments in cells that help to break down molecules and compounds. Without the LAMP2 protein, lysosomes can’t function properly and cellular debris builds-up. This buildup can cause issues including cardiomyopathy, muscle weakness, intellectual disabilities, eye disease and others.
Typically, males are more severely affected by this condition and develop symptoms at a younger age. Males have only one X chromosome — if they have the LAMP2 mutation or deletion on that chromosome, they may make insufficient amounts of the LAMP2 protein or, in some cases, none at all. Females, on the other hand, have two X chromosomes. If they have a mutation or deletion in one chromosome, the other may still produce enough LAMP2 protein to compensate for the defect. As a result, female patients present with greater variability of disease, ranging from having no signs or symptoms to being severely affected.
Symptoms and other features may include:
While symptoms described above may suggest the possibility of Danon Disease, genetic testing is needed to confirm a diagnosis of the condition.
Current treatments and interventions for Danon Disease address the symptoms and often require a team of specialists. This may include a combination of cardiologist, neurologist, ophthalmologist, geneticist, genetic counselor, rehabilitation physician, educational specialist, and physical therapist. There is no FDA-approved therapy known to cure or slow the underlying issues caused by LAMP2 protein deficiency.
Learn more about living with Danon Disease.
A disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body and can lead to heart failure. There are two types of cardiomyopathy that may present in Danon Disease.
Hypertrophic cardiomyopathy is the more common form and occurs when the heart muscle becomes abnormally thick (hypertrophied), making it harder for the heart to pump blood. In dilated cardiomyopathy, the ventricle of the heart stretches and thins (dilates) and is not able to pump blood as well as a healthy heart.
A new mutation (or deletion) in someone’s DNA that is not inherited from either parent. It may also be referred to as a sporadic or spontaneous mutation.
Lysosomal associated membrane protein 2 (LAMP2)
The LAMP2 gene provides instructions for the LAMP2 protein found in the walls of cells, known as lysosomes.
A compartment of the cell that contains digestive enzymes that break down excess or worn-out cell parts. Lysosomes play an important role in the recycling system of cells.
The X chromosome is one of two sex chromosomes. Females have two X chromosomes, while males have one X and one Y chromosome. Egg cells all contain an X chromosome, while sperm cells contain either an X or a Y chromosome.
The contents of the Danon Foundation website, such as text, graphics, images and other material are intended for informational and educational purposes only and not for the purpose of rendering medical advice. The contents of this website are not intended to substitute for professional medical advice, diagnosis or treatment. Although we take efforts to keep the medical information on our website updated, we cannot guarantee that the information on our website reflects the most up-to-date research.
Please consult your physician for personalized medical advice. Always seek the advice of a physician or other qualified healthcare provider with any questions regarding a medical condition. Never disregard or delay seeking professional medical advice or treatment because of something you have read on the Danon Foundation website.