Diagnosis and Treatment of Danon Disease | Endocrinology

Danon disease

What is Danon disease?

Danon disease is a condition branded by weakening of the heart muscle (cardiomyopathy); weakening of the muscles used for movement, called skeletal muscles, (myopathy); and intellectual disability. Males with glycogen storage disease Type IIb usually develop the disorder earlier than females and are more severely affected. Signs and symptoms begin in childhood or adolescence in most affected males and in early adulthood in most affected females. Pretentious males, on average, live to age 19, while affected females live to an average age of 34.

Cardiomyopathy is the most common symptom of Danon disease and arises in all males with the condition. Most pretentious men have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that may make it harder for the heart to pump blood. Other affected males have dilated cardiomyopathy, which is a disorder that weakens and enlarges the heart, preventing it from pumping blood efficiently.

Some pretentious men with hypertrophic cardiomyopathy later develop dilated cardiomyopathy. Either type of cardiomyopathy can lead to heart failure and premature death. Most women with glycogen storage disease Type IIb also progress cardiomyopathy; of the women who have this feature, about half have hypertrophic cardiomyopathy, and the other half have dilated cardiomyopathy.

Affected persons can have other heart-related signs and symptoms, including a sensation of fluttering or beating in the chest (palpitations), an abnormal heartbeat (arrhythmia), or chest pain. Many affected individuals have abnormalities of the electrical signs that control the heartbeat (conduction irregularities). People with Danon disease are often pretentious by a specific conduction abnormality known as cardiac preexcitation. The type of cardiac preexcitation most frequently seen in people with Danon disease is called the Wolff-Parkinson-White syndrome pattern.

Skeletal myopathy happens in most men with glycogen storage disease Type IIb and about half of affected women. The weakness typically occurs in the muscles of the upper arms, shoulders, neck, and upper thighs. Many males with Danon disease have raised levels of an enzyme called creatine kinase in their blood, which often indicates muscle disease.

Most men with Danon disease, but only a small percentage of pretentious women, have intellectual disability. If present, the disability is usually mild.

There can be other signs and symptoms of the illness in addition to the three characteristic features. Several affected those have had gastrointestinal disease, breathing problems, or visual abnormalities.

Who gets Danon disease?

Danon disease is a rare congenital disorder. Symptom presentation can occur at birth.

Both men and women can be affected, although men can develop the signs and symptoms in childhood. Rather, affected women generally develop symptoms in adulthood.

Around the world, people of all racial and ethnic groups can be affected.

Risk factors for Danon disease

A positive family history can be a major risk factor, as Danon disease can be inherited

Currently, no other risk factors for the disorder have been clearly identified.

It is important to note that having a risk factor does not mean that the condition will develop. A risk factor increases your chances of getting a condition compared to a person without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that a person will not develop the condition. It is always important to discuss the consequence of risk factors with your healthcare provider.

Symptoms of Danon disease

The symptoms of Danon disease vary from case to case and be depending on sex; In general, the condition is branded by cardiomyopathy, weakening of skeletal muscles, and intellectual disability. Men generally develop the signs and symptoms of the condition earlier than women and are more affected. In men, symptoms usually appear in childhood or adolescence, while women may not have symptoms until early adulthood.

Cardiomyopathy is the most shared symptom of Danon disease and occurs in all men with the condition. Most (90%) of affected men have hypertrophic cardiomyopathy, which causes the heart muscle to become thicker and stiffer than normal. A smaller number (10%) have dilated cardiomyopathy, which weakens and enlarges the heart.

Both of these conditions affect the heart’s ability to pump blood efficiently through the body and can cause serious complications, such as heart failure and premature death. Many women with Danon disease also develop cardiomyopathy. Of these females, about half progress hypertrophic cardiomyopathy and the other half develop dilated cardiomyopathy.

People with Danon disease may also have additional heart-related signs and symptoms, counting fluttering or thrashing in the chest (palpitations), abnormal heartbeats (arrhythmia), or chest pain. Many affected people also have abnormalities in the electrical signals that control the heartbeat (conduction abnormalities). The most common conduction abnormality seen in people with Danon disease is Wolff-Parkinson-White syndrome.

Most menfolk and about half of females with Danon disease also have skeletal myopathy. The muscles most affected are the back, upper arms, shoulders, neck, and thighs. Many men also have raised levels of an enzyme called creatine kinase (CPK) in their blood, which is an indicator of muscle disease.

Most men with Danon disease also have a mild intellectual disability. On the contrary, women tend to have normal intellectual development. Less common signs and symptoms, including gastrointestinal illnesses, respiratory problems, and vision abnormalities, may also be present.

This counter lists the symptoms that people with this disease may have. For most diseases, symptoms vary from person to person. People with the same disease may not have all of the listed symptoms. This evidence comes from a database called Human Phenotype Ontology (HPO). The HPO collects information about symptoms that have been pronounced in medical resources. The HPO is occasionally updated. Use the HPO ID to access more detailed information about a symptom.

Causes of Danon disease

Danon disease is caused by mutations in the LAMP2 gene, which contains instructions for the production of an enzyme called lysosome-associated membrane protein 2 (LAMP-2). This enzyme is believed to help with the transport of cellular material to the cell’s lysosomes, where the materials are normally broken down and recycled. Mutations in the LAMP2 gene disrupt this process, leading to an abnormal accumulation of material that ultimately inhibits function and leads to Danon disease.

Each human cell contains two sex chromosomes. Men have an X chromosome and a Y chromosome in each of their cells. Females have two X chromosomes. Danon disease is a hereditary condition located on the X chromosome. A single mutated gene on the X chromosome in males is enough to cause a severe form of Danon disease. Because girls have two X chromosomes and an additional non-mutated gene on the X chromosome can reduce the severity of the disease, Danon disease is usually less severe in girls.

Diagnosis of Danon disease

Because Danon disease is rare and unknown to most doctors, the diagnosis is difficult and time-consuming. The diagnosis is suggested on the basis of a family history compatible with dominant X-linked inheritance and symptoms in affected relatives (cardiomyopathy, skeletal myopathy, intellectual disability, Wolff-Parkinson White, etc.). In some men, a skeletal muscle biopsy is performed in an effort to determine the cause of the muscle weakness.

If, in the course of examination of the biopsy materials, accumulation of glycogen and / or empty spaces appear in the cells of muscle tissue (vacuolization), Danon disease should be considered. This is also true for the analysis of a heart biopsy. A muscle biopsy that shows evidence of glycogen accumulation and empty spaces in muscle cells are key signs and indications that a diagnosis of Danon disease is a high probability.

It is important to know that, in the early stages of Danon disease, and probably also in women, muscle biopsy may be nonspecific. Therefore, a normal or nonspecific muscle biopsy does not exclude Danon disease. If there are other features of Danon disease, a non-diagnostic muscle biopsy should not discourage more definitive genetic testing. Patients who appear to have Pompe disease (based on muscle biopsy, for example) but have normal acid maltase activity should be screened for Danon disease. Unexplained hypertrophic cardiomyopathy in men is probably due to Danon disease in some people.

Antibodies to the LAMP-2 protein are available and tissue staining (from a muscle biopsy) for the absence of the LAMP-2 protein is another potential diagnostic approach, but not widely available. The LAMP-2 antibody test is probable to be normal in women with Danon disease and, if performed, should be understood with caution due to the potential for a false negative result.

Genetic testing of the LAMP2 gene is presently the gold standard for diagnosis and is available from particular genetic laboratories. Most of the genetic mutations that cause Danon disease predict summary levels or even nonappearance of the LAMP2 gene product, the LAMP-2 protein. Although the sensitivity of LAMP2 genetic testing is not known at this time, it is the best available. The non-invasive nature of DNA-based testing and the presence of LAMP2 gene tests in genetic diagnostic panels for hypertrophic cardiomyopathy favor this technique as the most common route to diagnosis.

Treatment for Danon disease

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

Complications

Complications of Danon disease can include:

  • Severe movement difficulties, particularly in men
  • Abnormal heart function
  • Heart failure
  • Complications can occur with or without treatment and, in some cases, also due to treatment

Prevention

Danon disease may not be preventable as it is a genetic disorder.

Genetic testing of prospective parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, can help better understand risks during pregnancy.

If there is a family history of the condition, genetic counseling will help assess risks before planning for the arrival of a child.

Active research is currently underway to explore the possibilities of treatment and prevention of inherited and acquired genetic disorders.

Regular medical examinations are recommended at regular intervals with tests and physical examinations.

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