User talk:Shifazainab1

INTRODUCTION
Danon disease is a metabollic disorder.It is associated with heart muscle abnormalities resembling severe hypertropic cardiomyopathy. It is a condition characterised by weakening of the heart muscle,weakening of the muscles used for movement and intellectual disability. Males with Danon disease develop conditions earlier than females. Cardiomyopathy is the most common symptom of Danon disease and occurs with males with the condition.[1]

HISTORY
Danon disease was characterized by Moris Danon in 1984.The first description of Danon Disease was in 1981 when 2 boys with heart and skeletal muscle disease (muscle weakness) and mental retardation were described. The first case reported in the Middle East was a family diagnosed with Danon Disease in the eastern region of United Arab Emirates with a new LAMP2 mutation, where 6 males were diagnosed as Danon disease patients and 5 female were diagnosed as carriers; making this family the largest one with patients and carriers of Danon disease.[2]
 * 1) REDIRECT []
 * 2) REDIRECT []

SYMPTOMS
In males the symptoms of Danon Disease are more severe.
 * An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence).
 * The muscle weakness can be severe and can affect endurance and even the ability to walk.
 * The heart disease can be severe and can lead to a need for medications.
 * Problems with the electrical conduction in the heart can occur.

In females the symptoms of Danon Disease are less severe. Problems with the electrical condution in the heart can occur.[3]
 * Learning problems and mental retardation are usually absent.
 * Muscle weakness is often absent or subtle. Some females will tire easily with exercise.
 * Heart muscle disease (cardiomyopathy) is often absent in girls and some women will develop this in adulthood.

GENETICS
Danon disease is caused by mutations in the LAMP2 gene. The LAMP2 gene provides instructions for making a protein called lysosomal associated membrane protein-2 (LAMP-2),is found in the membrane of cellular structures called lysosomes. Lysosomes are compartments in the cell that digest and recycle materials. The role the LAMP-2 protein plays in the lysosome is unclear. The transport of cellular materials into lysosomes requires the formation of cellular structures called autophagic vacuoles, which then attach to lysosomes. The LAMP-2 protein may be involved in the fusion between autophagic vacuoles and lysosomes. Mutations in the LAMP2 gene lead to the production of very little LAMP-2 protein, which may impair the process of transporting cellular material into the lysosome. People with Danon disease have an abnormally large number of autophagic vacuoles in their muscle cells. It is possible that this accumulation leads to breakdown of the muscle cells, causing the muscle weakness seen in Danon disease.[4]

HOW DO PEOPLE INHERIT DANON DISEASE
This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females, a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males, a mutation in the only copy of the gene in each cell causes the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[5]

METABOLIC PATHWAY
"Lysosomal glycogen storage disease with normal acid maltase", is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. We report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease.[6]

TREATMENT
SURGICAL METHOD Implantable loop recorder (ILR) This device is implanted under the skin to record any arrhythmias that may happen when cardiovascular symptoms occur. The usual indication is an assessment of severe symptoms that occur too infrequently to be recorded by using conventional, external event recorders. It can be automatically activated when the programmed parameters of the device are satisfied. It can also be activated when the patient has symptoms. An activator that the patient carries is placed over the device, and a button is pushed to activate the ILR. ICD placement After Danon disease and severe hypertrophic changes of the heart are diagnosed, placement of an ICD should be considered. For patients who have the dilated form of cardiomyopathy, ICDs is indicated because of the degree of their dysfunction and their history of arrhythmias. Recommendations from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trial apply to these patients.[7]