Danon Disease

By Haley Miller

The Cellular Problem

Cellular Problem

- In cellular vacuoles, in muscle mainly

- Vacuoles function: They store food and nutrients or waste and move things around the cell. They isolate materials that might be harmful or a threat to the cell. They also play a role in communication in cells, and have a major role in autophagy, which is maintaining a balance between production and degradation or turnover of many substances.

- Danon disease is caused by mutations in the LAMP2 gene. This gene provides instructions for making a protein called lysosomal associated membrane protein-2 (LAMP-2), which is found in the membrane of lysosomes, this protein may help transport cellular materials or digestive enzymes into the lysosome. This transportation requires the formation of autophagic vacuoles, which later attach to lysosomes. Without this gene vacuoles can't communicate to vesicles or lysosomes.



http://ghr.nlm.nih.gov/condition/danon-disease

Inheritance

The inheritance pattern of Danon disease is X-linked dominant, which means that the gene causing the disease is located on an X chromosome. A person needs only one copy of the affected X chromosome to develop symptoms. Men have only one X chromosome, so they always develop the disease. They develop it at an earlier age and in a more severe form than women. Women have two X chromosomes and only one of them is affected, so they develop symptoms later in life. A woman who carries the mutated gene has a 50 percent chance of passing it on to her children. Men with the affected gene pass on the disease to all their daughters, while their sons never develop the disease as they inherit only a Y chromosome from their fathers.


http://www.socialstyrelsen.se/rarediseases/danondisease#anchor_6


Some Signs

-feeling of fluttering

-pounding in the chest (palpitations)

-abnormal heartbeat (arrhythmia)

-higher levels of an enzyme called creatine kinase in blood

-chest pain


Symptoms



In males:

  • Some learning problems or mental retardation

  • Muscle weakness can be severe and can affect endurance or even the ability to walk

  • The heart disease can be severe and can lead to a need for medications. The heart disease may require a heart transplant or can lead to death

  • Problems with the electrical conduction in the heart can occur. A form of this conduction problem is called 'Wolff-Parkinson-White' syndrome. This may also be a form of cardiac preexcitation, which is when nerves in the heart send impulses to quickly or early.

  • The symptoms are usually progressive in boys and tend to gradually get worse

  • Some boys may have problems with their vision or a problem with the pigment in their retinas

  • Can lead to heart failure and early death


In females:

  • In females the symptoms of Danon Disease are less severe than males.

  • Muscle weakness is often absent or subtle. Some females may tire easily with exercise

  • Heart muscle disease (cardiomyopathy) is often absent in girls and some women will develop this disease when they reach adulthood

  • Problems with the electrical conduction in the heart can occur. Sometimes the conduction problem is called 'Wolff-Parkinson-White' syndrome. This may also be a form of cardiac preexcitation, which is when nerves in the heart send impulses to quickly or early.

  • Symptoms in females progress more slowly than in males. Heart disease may not be a problem for females until adulthood

  • Some females may also have problems with their vision or a problem with the pigment in the back of their retinas
  • Can lead to heart failure and early death


http://www.danondisease.org/id2.html

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Diagnosis

In males, typical symptoms of heart failure, muscular weakness and mild cognitive impairment lead to a suspected diagnosis of Danon disease. The diagnosis can be confirmed with the help of a tissue analysis, a DNA analysis, a 24-hour ECG (electrocardiogram), and blood tests. A 24-hour ECG (electrocardiogram) test is carried out on the heart and also sometimes ultrasound and MRI (magnetic resonance imaging) examinations. Danon disease may be present if irregularities in the electrical impulses of the heart and irregular cardiac rhythms are found. It may also be if the heart is enlarged and the heart muscle is thickened, especially the wall between the two chambers of the heart and the wall of the left ventricle. At a later stage the heart becomes weakened and further enlarged (dilated cardiomyopathy). Blood tests reveal signs of heart failure and damage to muscle fibres. Tissue samples from either the skeletal or cardiac muscles show an accumulation of glycogen, and fluid-filled blisters in cells (vacuoles). Muscle tissue is also analysed to see if LAMP2 protein is present in muscle fibres. An absence of LAMP2 indicates a definite diagnosis. The diagnosis can also be confirmed by DNA analysis.

http://www.socialstyrelsen.se/rarediseases/danondisease#anchor_6

Treatment

As of now there is no cure for Danon disease. Doctors focus on alleviating symptoms and providing quality care to patients. Treatment is usually carried out in a hospital or other medical department. Certain types of arrhythmia, abnormal heart beat, can be treated by a procedure where a catheter is threaded through a patient’s blood vessels to reach the heart so that those parts of the heart where the abnormal impulses originate can be treated by freezing or using radio waves. However, medication or processes to treat arrhythmia has little effect on Danon disease. Many consider a heart transplant and it is recommended by doctors for patients with Danon disease, but it can be a very dangerous surgery. There is no cure or enough data collected to show the best methods of treatment for Danon disease because of how rare it is. It may cause severe lack of mobility and retardation, significantly effecting the patients lifestyle. But whether this disease is treated or not it still has the potential to cause heart failure and death.


http://www.socialstyrelsen.se/rarediseases/danondisease#anchor_6