Danon disease

Danon disease is a rare genetic disorder that primarily affects the heart, skeletal muscles, and eyes. It is classified as a type of lysosomal storage disease and is caused by mutations in the LAMP2 gene. The disease is named after Dr. Morlie Danon, who first described it in 1981.

Genetics

Danon disease is inherited in an X-linked dominant manner. This means that the mutated gene responsible for the disorder is located on the X chromosome, and a single copy of the mutated gene is sufficient to cause the disease in males (who have one X and one Y chromosome). Females (who have two X chromosomes) can also be affected, but they typically have a milder form of the disease due to the presence of a second, normal copy of the gene.

The LAMP2 gene encodes the lysosome-associated membrane protein 2, which is essential for the normal function of lysosomes. Lysosomes are cellular organelles that break down waste materials and cellular debris. Mutations in the LAMP2 gene disrupt the normal function of lysosomes, leading to the accumulation of autophagic vacuoles in cells, particularly in cardiac muscle, skeletal muscle, and retinal cells.

Clinical Features

The clinical presentation of Danon disease can vary widely, but common features include:

• Cardiomyopathy: This is the most severe manifestation and can include hypertrophic cardiomyopathy or dilated cardiomyopathy. Symptoms may include heart failure, arrhythmias, and sudden cardiac death.
• Skeletal muscle weakness: Patients may experience progressive muscle weakness and exercise intolerance.
• Retinopathy: Visual disturbances and retinal abnormalities can occur, potentially leading to vision loss.
• Intellectual disability: Some patients may have mild to moderate intellectual disability.

Diagnosis

Diagnosis of Danon disease typically involves a combination of clinical evaluation, family history, and genetic testing to identify mutations in the LAMP2 gene. Additional diagnostic tools may include:

• Electrocardiogram (ECG) and echocardiogram to assess cardiac function.
• Muscle biopsy to examine muscle tissue for characteristic vacuoles.
• Ophthalmologic examination to detect retinal abnormalities.

Treatment

There is currently no cure for Danon disease, and treatment is primarily supportive and symptomatic. Management strategies may include:

• Cardiac care: Medications to manage heart failure and arrhythmias, and in severe cases, heart transplantation.
• Physical therapy: To maintain muscle strength and function.
• Ophthalmologic care: Regular eye examinations and interventions as needed for visual disturbances.

Prognosis

The prognosis for individuals with Danon disease varies depending on the severity of the cardiac involvement. Males typically have a more severe course of the disease and may experience significant cardiac complications in their teens or early adulthood. Females generally have a milder form of the disease but can still experience significant health issues.

Related Pages

• Lysosomal storage disease
• Cardiomyopathy
• X-linked dominant inheritance
• LAMP2 gene
• Hypertrophic cardiomyopathy
• Dilated cardiomyopathy