Mucopolysaccharidosis type II; Hunter syndrome ... (Mucopolysaccharidosis type II, Hunter syndrome) - Gen IDS.
Mucopolysaccharidoses encompass a group of inherited metabolic diseases caused by the absence or malfunction of certain necessary for processing glycosaminoglycans, found in bone, cartilage, tendons, corneas, skin and connective tissue enzymes. The glycosaminoglycans, formerly known as mucopolysaccharides, are also present in the synovial fluid of the joints. People suffering from mucopolysaccharidosis not encode sufficient quantities of one of the eleven enzymes required to transform glycosaminoglycans in protein and simpler molecules, or encode enzymes that do not work properly. Over time, these glycosaminoglycans accumulate in cells, blood and connective tissues. This produces permanent and progressive cellular damage that affect the appearance and physical abilities, organs and body functions of the individual and, in most cases, mental development.
Type II (MPS II) mucopolysaccharidoses, also known as Hunter syndrome is a disease that affects many different parts of the body and occurs almost exclusively in males. Despite being a progressive debilitating disease, rate of progression varies among affected individuals. In general, people with MPS II show no characteristic of the disease at birth, but begin to show signs and symptoms between 2 and 4 years old. These signs and symptoms may include enlargement of facial features (development of thick lips, big cheeks rounded, broad nose and macroglosia). The vocal cords are also enlarged, which leads to severe hoarse voice. In addition, the narrowing of the airways causes frequent respiratory infections and sleep apnea. As the disease progresses, people need medical care to keep your airway open. Other signs and symptoms may include microcephaly, hydrocephalus, hepatosplenomegaly, umbilical hernia or inguinal hernia, thick and slightly elastic skin growths white skin that look like pebbles, hearing loss, recurrent ear infections, problems with the retina that reduce vision , carpal tunnel syndrome, spinal stenosis in the neck that can compress and damage the spinal cord and heart valve problems. Abnormalities in heart valves can lead to ventricular hypertrophy and eventually can lead to heart failure.
Children with MPS II grow steadily until about 5 years old and subsequently slows growth and short stature. In addition, people with this disease have joint deformities that significantly affect mobility. Most people with MPS II also have multiple dysostosis, including a generalized thickening of most long bones, especially the ribs.
They described two types of MPS II, called the major and minor types. While both types affect many organs and different tissues, people with severe MPS II also show a decline in intellectual function and a faster progression of the disease. Individuals with severe form begin to lose basic functional skills between 6 and 8 years old. The life expectancy of these people is 10 to 20 years. For its part, individuals with mild MPS II also have a lower life expectancy, but usually live into adulthood and intelligence is not affected. Heart disease and obstruction of the airways are major causes of death in people with both types of MPS II.
This process is due to mutations in the gene IDS (iduronate sulfatase 2-), located on the long arm of the X chromosome (Xq28). This gene encodes an enzyme called iduronate 2-sulfatase (I2S), which is essential for the breakdown of glycosaminoglycans (GAG). Specifically, I2S sulfate eliminates a molecule of alpha-L-iduronic sulfated, which is present in two GAGs called heparan sulfate and dermatan sulfate. Within cells, I2S is in the lysosomes.
Have identified at least 478 mutations in the IDS gene which: missense mutations (244), and cutting mutations -splicing- junction (44), small deletions (87), small insertions (39), small indels (9), larger deletions (37), insertions / higher duplications (4) and complex rearrangements (14). All mutations reduce or completely eliminate the function of I2S. Mutations that result in the complete absence of I2S cause the most severe form of the disease. The absence of activity of the enzyme results I2S accumulation of heparan sulfate and dermatan sulfate in the interior of cells, specifically in the lysosomes. Due to the accumulation of molecules within lysosomes, this disease is considered an alteration of lysosomal storage. Accumulation of GAG increases the size of the cells, so many tissues and organs are enlarged. Furthermore, glycosaminoglycans likely interfere with the functions of other proteins in lysosomes and alter the movement of molecules within the cell.
This disease is inherited in a recessive X - linked pattern in males, who have only one X chromosome, an altered copy of the gene in each cell it is sufficient to express the disease. In females, having two X chromosomes, a mutation would have to occur in both copies of the gene to express the disease. Because it is unlikely that women have two altered copies of this gene, males are affected by X - linked recessive disorders much more frequently 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 Mucopolysaccharidosis type II (MPS II), by complete PCR amplification of the exons of the IDS 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).