What are the other Names for this Condition? (Also known as/Synonyms)

• Antopol Disease
• Glycogen Storage Cardiomyopathy
• X-Linked Vacuolar Cardiomyopathy and Myopathy

What is Danon Disease? (Definition/Background Information)

• Danon Disease is a rare genetic condition characterized by weakening of the heart muscle (cardiomyopathy), weakening of the muscles used for movement (skeletal muscles myopathy), and intellectual disability
• This condition is a type of lysosomal storage disorder. Lysosomes are compartments within the cell that use enzymes to break down large molecules into smaller ones that the cell can use
• In Danon Disease there is a defect in the wall (membrane) of the lysosome. The defect is caused by mutations in the LAMP2 gene
• Danon Disease is inherited in an X-linked dominant pattern. As a result, males tend to be more severely affected than females and develop symptoms at a younger age
• Treatment is aimed at addressing the symptoms present in each individual and may require a team of specialists

(Source: Danon Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Danon Disease? (Age and Sex Distribution)

• Danon Disease is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected, although males may develop the signs and symptoms in childhood. In contrast, affected females generally develop symptoms in adulthood
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Danon Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since Danon Disease can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Danon Disease? (Etiology)

• Danon Disease is caused by mutation in the LAMP2 gene. LAMP2 stands for “lysosomal-associated membrane protein 2
• Danon Disease is inherited in an X-linked dominant pattern

(Source: Danon Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

X-linked dominant inheritance pattern: In this type of inheritance, the defective gene is carried on the X chromosome. A single copy of the defective gene in each cell of an individual is sufficient for the disease to manifest itself. Since males have only one X chromosome inherited from their mother, the defective gene is expressed in them, causing the condition. Although females carry two X chromosomes, the unaffected gene copy in the normal X chromosome does not completely mask the effects of a defective gene copy.

What are the Signs and Symptoms of Danon Disease?

The signs and symptoms of Danon Disease may vary, depending on the affected individual’s gender and include:

• Cardiomyopathy:
  • Most (90%) affected men have hypertrophic cardiomyopathy
  • Many women with Danon Disease also develop cardiomyopathy. Of these women, about half develop hypertrophic cardiomyopathy and the other half develop dilated cardiomyopathy
• Fluttering or pounding in the chest (palpitations)
• An abnormal heartbeat (arrhythmia) 
• Chest pain
• Abnormalities of the electrical signals that control the heartbeat (conduction abnormalities). The most common conduction abnormality seen in individuals with Danon disease is Wolff-Parkinson-White syndrome
• Skeletal myopathy in affected men: The muscles most often affected are those in the back, upper arms, shoulders, neck, and thigh 
• Elevated levels of an enzyme called creatine kinase (CPK, an indicator of muscle disease) in the blood of affected men 
• Mild intellectual disability in men
• Gastrointestinal disease
• Breathing problems
• Vision abnormalities
• Arrhythmia
• Cardiomegaly
• Cognitive impairment
• Cardiorespiratory arrest
• Elevated serum creatine phosphokinase
• EMG: Myopathic abnormalities
• Exercise intolerance; exercise-induced muscle cramps
• Generalized amyotrophy
• Global developmental delay
• Gait disturbance
• Hypertrophic cardiomyopathy
• Hypokinesia
• Intellectual disability
• Muscle flaccidity
• Myocardial fibrosis
• Myocardial necrosis
• Pes cavus
• Proximal muscle weakness
• Visual impairment

(Source: Danon Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Danon Disease Diagnosed?

Danon Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm LAMP2 gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Danon Disease?

The complications of Danon Disease may include:

• Severe movement difficulty, particularly in men
• Abnormal heart function
• Heart failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Danon Disease Treated?

The treatment for Danon Disease is aimed at addressing the symptoms present in each individual. This may require a team of specialists in addition to the primary care physician, including a cardiologist, neurologist, ophthalmologist, geneticist, genetic counselor, rehabilitation physician, educational specialist, and physical therapist.

• Because Danon Disease can be associated with rapidly progressive cardiomyopathy and sudden death, careful monitoring of heart disease is required. Medications for heart disease may be a first line of treatment
• Aggressive interventions may be recommended for people showing signs of progressive heart failure (e.g., early intervention with heart transplantation or implantable cardioverter-defibrillator)
• Assessment of muscle strength should be performed regularly
• Physical therapy may help maintain muscle strength and flexibility
• Males with intellectual disabilities should receive appropriate educational interventions

(Source: Danon Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Danon Disease be Prevented?

Danon Disease may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Danon Disease? (Outcomes/Resolutions)

• The prognosis of Danon Disease is guarded, owing to serious abnormalities in the structure and function of the heart
• The average lifespan for affected males and females is 19 and 34 years, respectively

Additional and Relevant Useful Information for Danon Disease:

Danon Disease is also known by the following names:

• Glycogen Storage Disease limited to the Heart
• Glycogen Storage Disease Type 2b (formerly)
• GSD2B (formerly)
• Lysosomal Glycogen Storage Disease without Acid Maltase Deficiency (formerly)
• Pseudoglycogenosis 2

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/