Danon disease is a condition characterized by weakening of the heart muscle (cardiomyopathy); weakening of the muscles used for movement, called skeletal muscles (myopathy); and intellectual disabilities. People with Danon disease may develop the condition at different ages. Signs and symptoms of this condition appear about 15 years earlier in males than in females. Males first experience health problems in childhood or adolescence; without treatment, these individuals typically live into early adulthood. Females start experiencing health problems in early adulthood and typically survive into mid-adulthood without treatment.

Danon disease is caused by variants (also called mutations) in the LAMP2 gene. The LAMP2 gene provides instructions for making a protein called lysosome-associated membrane glycoprotein 2 (LAMP-2). As its name suggests, this protein is found in the membrane of cellular structures called lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of materials. The LAMP-2 protein helps transport cellular materials or digestive enzymes into the lysosome. Three slightly different versions (isoforms) of the LAMP-2 protein are produced. These isoforms have slightly different functions and are found in different tissues throughout the body. The main isoform is needed to transport materials into lysosomes using a formation of cellular structures called autophagic vacuoles (or autophagosomes). Cellular material is first enclosed in an autophagic vacuole inside the cell. The vacuole then attaches (fuses) to a lysosome to transfer the cellular material into the lysosome. The LAMP-2 protein is  involved in the fusion between autophagic vacuoles and lysosomes.

Danon disease is a rare condition, but the exact prevalence is unknown.

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome) a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome) one altered copy of the gene can cause the condition, although the features may be less severe than in people with both copies altered. Some people with only one altered copy of the gene may have no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Published Date: April 18, 2024
Published By: National Institutes of Health