Danon Disease

Danon disease is a rare inherited disorder that affects many organ systems, especially the cardiovascular, skeletal, and central nervous systems. The condition is one of about 50 lysosomal storage disorders (LSD) in which genetic variations disrupt the normal activity of lysosomes in human cells.

Lysosomes in human cells contain specific proteins known as enzymes that are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not contain one of these enzymes in sufficient quantities to break down molecules for cells to function properly.

Children with Danon disease typically begin displaying symptoms in childhood or adolescence. Boys tend to develop signs and symptoms earlier, and they often have more severe symptoms than girls.

Symptoms may include:

• Weakening of the heart muscle (cardiomyopathy)
• Weakening of the skeletal muscles (myopathy)
• Intellectual disability
• Stomach problems
• Difficulty breathing
• Visual abnormalities

Danon disease is caused by mutations in the LAMP2 gene, which contains instructions for the production of an enzyme called lysosomal associated membrane protein-2 (LAMP-2). This enzyme is thought to assist with the transportation of cellular material into the lysosomes of the cell, where the materials are normally broken down and recycled. Mutations in the LAMP2 gene impair this process, leading to an abnormal accumulation of material that eventually inhibits function and leads to Danon disease.

Every human cell contains two sex chromosomes. Males have one X chromosome and one Y chromosome in each of their cells. Females have two X chromosomes. Danon disease is a genetic condition located on the X chromosome. A mutated gene on the lone X chromosome in males is sufficient to cause a severe form of Danon disease. Because girls have two X chromosomes and a non-mutated gene on the additional X chromosome may reduce the severity of the disease, Danon disease is often less severe in girls.

There are currently no approved treatments to reverse the effects of Danon disease. Instead, doctors treat specific symptoms to reduce the impact of the disease.

At the Boston Children’s Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we partner with you and your child to provide multifaceted care in our BoLD clinic. We work with a broad array of world-class specialists at Boston Children’s to help achieve the greatest possible quality of life for families managing a diagnosis of Danon disease.