What is Danon Disease?

Danon Disease is a rare, inherited disorder that affects many organ systems in the body. Danon Disease affects males more frequently than females. Untreated, the condition is fatal.

Among males, the condition often results in a defective heart, weakening of muscles in the body, and mild to severe intellectual disabilities. A heart transplant is usually needed during childhood or early adolescence.

Among females, the condition is generally milder with fewer symptoms. Onset might not occur until early adulthood. Sometimes a heart transplant is required to treat the condition.

Common synonyms for Danon Disease:

• Pseudoglycogenosis II
• Glycogen storage cardiomyopathy
• GSD IIB
• Vacuolar cardiomyopathy and myopathy, X-linked
• Glycogen storage disease type IIB
• Antopol disease
• Lysosomal glycogen storage disease without acid maltase deficiency
  
  

  Symptoms

  Danon Disease is not usually detected at birth. However, noticeable symptoms arise over time. These symptoms range from mild to severe. Males tend to experience more serious symptoms and earlier onset of symptoms. Females tend to experience milder symptoms that begin during early adulthood.

  Danon Disease symptoms include:

  • Diminished motor skills.
  • Impaired heart muscle, or cardiomyopathy.
  • Ongoing stomach issues.
  • Persistent breathing problems.
  • Intellectual challenges or learning problems.
  • Weakened skeletal muscles, or myopathy.
  • Visual abnormalities that impact sight.

Causes

A mutation of a gene known as LAMP2 is the main cause of Danon Disease. LAMP2 is an acronym that stands for lysosomal associated membrane protein-2. Essentially, the LAMP2 gene produces a specific protein.

These proteins are housed in lysosomes, cellular compartments that digest and reuse cellular material. No one knows the exact Danon Disease cause. However, researchers believe that abnormalities in LAMP2 genes result in reduced production of these proteins, limiting transportation of cellular material into lysosomes.

The breakdown of transportation slows down other processes in the cellular compartments. A domino effect of abnormal functioning then leads to a buildup of autophagic vacuoles. Doctors believe the accumulation of autophagic vacuoles in muscle cells is responsible for the muscle weakness experienced with Danon Disease.

Diagnosis

Since Danon Disease is rare, diagnosis is often complicated. A diagnosis often involves a review of your medical history and symptoms, a physical exam, and various tests.

Doctors often use the following tests to make a Danon Disease diagnosis:

• Genetic testing of the LAMP2 Gene—Genetic testing is the most common diagnostic test for Danon Disease. Possible genetic testing includes single-gene testing, multigene panel, exome sequencing, and genome sequencing.
• Skeletal muscle biopsy—Your doctor will remove cells from your muscles and analyze them under special microscopes. Doctors look for an accumulation of glycogen and gaps in the muscle cells, both indicators of Danon Disease.
• Heart biopsy—Your doctor will remove a tiny sample of tissue from your heart to test in a laboratory setting.

Treatment & Recovery

Treatment for Danon Disease often involves a team of specialists, close monitoring, medication, and surgery. Your doctor may also recommend physical therapy to strengthen weakened muscles and educational support to treat learning disabilities. The most common surgery is a heart transplant, sometimes called a Danon Disease heart transplant.

Specialists involved in your treatment can include:

• Cardiologists
• Geneticists
• Physical Therapists
• Neurologists
• Genetic Counselors
• Education Specialists
• Rehabilitation Physicians

Danon Disease prognosis depends on the severity of the condition and symptoms. Untreated, the condition can be fatal.

Investigative Therapies

Research into future, investigative therapies is ongoing. One avenue of research is likely to focus on the biochemical role of the LAMP2 gene. New therapies might arise from increased knowledge of the gene’s function in the development of the disease.

Another possible future approach is protein replacement therapy to replace the missing LAMP2 protein. Doctors have successfully treated other diseases associated with missing proteins using this therapy.

Complications

Left untreated, an individual with Danon Disease is likely to experience complications. Some of these complications can be severe, even fatal.

Danon Disease complications may include:

• Heart problems—You may feel an irregular or abnormal heart rhythm.
• Heart failure—Your heart may stop working. This requires immediate medical attention.
• Premature death—Early death is possible with Danon Disease.
• Vision problems—Danon Disease may affect visual functioning.
• Intellectual problems—Learning challenges or disabilities may occur that make schooling more difficult. Educational support might be needed.
• Muscle weakness—Danon Disease can weaken muscles and diminish motor skills. Over time, individuals may experience more difficulty with movement such as standing, walking, or running.

If you or a loved one experience any of the signs and symptoms of Danon Disease, please contact a heart specialist at Baptist Health today.

Causes

A mutation of a gene known as LAMP2 is the main cause of Danon Disease. LAMP2 is an acronym that stands for lysosomal associated membrane protein-2. Essentially, the LAMP2 gene produces a specific protein.

These proteins are housed in lysosomes, cellular compartments that digest and reuse cellular material. No one knows the exact Danon Disease cause. However, researchers believe that abnormalities in LAMP2 genes result in reduced production of these proteins, limiting transportation of cellular material into lysosomes.

The breakdown of transportation slows down other processes in the cellular compartments. A domino effect of abnormal functioning then leads to a buildup of autophagic vacuoles. Doctors believe the accumulation of autophagic vacuoles in muscle cells is responsible for the muscle weakness experienced with Danon Disease.

Diagnosis

Since Danon Disease is rare, diagnosis is often complicated. A diagnosis often involves a review of your medical history and symptoms, a physical exam, and various tests.

Doctors often use the following tests to make a Danon Disease diagnosis:

• Genetic testing of the LAMP2 Gene—Genetic testing is the most common diagnostic test for Danon Disease. Possible genetic testing includes single-gene testing, multigene panel, exome sequencing, and genome sequencing.
• Skeletal muscle biopsy—Your doctor will remove cells from your muscles and analyze them under special microscopes. Doctors look for an accumulation of glycogen and gaps in the muscle cells, both indicators of Danon Disease.
• Heart biopsy—Your doctor will remove a tiny sample of tissue from your heart to test in a laboratory setting.

Treatment & Recovery

Treatment for Danon Disease often involves a team of specialists, close monitoring, medication, and surgery. Your doctor may also recommend physical therapy to strengthen weakened muscles and educational support to treat learning disabilities. The most common surgery is a heart transplant, sometimes called a Danon Disease heart transplant.

Specialists involved in your treatment can include:

• Cardiologists
• Geneticists
• Physical Therapists
• Neurologists
• Genetic Counselors
• Education Specialists
• Rehabilitation Physicians

Danon Disease prognosis depends on the severity of the condition and symptoms. Untreated, the condition can be fatal.

Investigative Therapies

Research into future, investigative therapies is ongoing. One avenue of research is likely to focus on the biochemical role of the LAMP2 gene. New therapies might arise from increased knowledge of the gene’s function in the development of the disease.

Another possible future approach is protein replacement therapy to replace the missing LAMP2 protein. Doctors have successfully treated other diseases associated with missing proteins using this therapy.

Complications

Left untreated, an individual with Danon Disease is likely to experience complications. Some of these complications can be severe, even fatal.

Danon Disease complications may include:

• Heart problems—You may feel an irregular or abnormal heart rhythm.
• Heart failure—Your heart may stop working. This requires immediate medical attention.
• Premature death—Early death is possible with Danon Disease.
• Vision problems—Danon Disease may affect visual functioning.
• Intellectual problems—Learning challenges or disabilities may occur that make schooling more difficult. Educational support might be needed.
• Muscle weakness—Danon Disease can weaken muscles and diminish motor skills. Over time, individuals may experience more difficulty with movement such as standing, walking, or running.

If you or a loved one experience any of the signs and symptoms of Danon Disease, please contact a heart specialist at Baptist Health today.