Glycogenosis Type IIB (Danon disease) (Danon disease) - Gen LAMP2.
Danon's disease is a disorder characterized by cardiomyopathy, myopathy and intellectual disabilities. Generally, men with this disease develop the disorder earlier than women and are more intensely affected.
Signs and symptoms begin in childhood or adolescence in boys and early adulthood in women. Affected men on average live to 19 years, while women affected live to an average age of 34 years. Cardiomyopathy is the most common symptom of the disease Danon and appears in all men with the disease. Males often suffer hypertrophic cardiomyopathy, while others suffer from dilated cardiomyopathy. Either cardiomyopathies can lead to heart failure and premature death. Most women with the disease also develop cardiomyopathy. Of these, about half have hypertrophic cardiomyopathy, and the other half dilated cardiomyopathy.
Affected individuals may have other heart - related, such as palpitations, arrhythmia or chest pain symptoms. Many of those affected with cardiac conduction abnormalities, such as heart preexcitation (Wolff-Parkinson-White). Skeletal myopathy occurs in most males and about half of the women affected, affecting the muscles of the upper arms and neck. Many of the men with Danon disease have elevated levels of creatine kinase enzyme in blood, which usually indicates the existence of muscular disease. Most men and a small percentage of women affected have intellectual disabilities. If present, disability is usually mild or moderate in males and in females slightly.
Danon disease is caused by mutations in the gene LAMP2, located on the long arm of chromosome X (Xq24). This gene encodes the protein LAMP-2, located in the membrane of lysosomes, which participate in the transport of cellular materials or enzymes in the lysosome through the formation of autophagic vacuoles. Protein LAMP-2 would be involved in the fusion of the autophagic vacuoles and lysosomes.
Mutations in the gene cause LAMP2 absence or low protein production, which can impair the transport process of cell material in the lysosome. Cells without the protein, the fusion of lysosomes and autophagic vacuoles occurs more slowly, which may lead to accumulation of autophagic vacuoles. People with Danon disease have an abnormally large number of autophagic vacuoles in their muscle cells. This accumulation may lead to the breakdown of muscle cells, causing muscle weakness characteristic.
This disease is inherited as a dominant X - linked pattern in women who have two X chromosomes, a mutation in one of the two copies of the gene in each cell it is sufficient to cause the disorder. In males, who have only one X chromosome, a mutation in the single gene copy in each cell causes alteration. Therefore, in most cases, men report more severe symptoms of the disease than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Danon disease, by complete PCR amplification of exons LAMP2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).