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Hunter syndrome, or mucopolysaccharoidosis Type II, is a lysosomal storage disease caused by a deficient (or absent) enzyme, iduronate-2-sulfatase (I2S).[1] The syndrome is named after physician Charles A. Hunter (1873-1955), who first described it in 1917.[2][3] Born in Scotland, Hunter emigrated to Canada and had a medical practice in Winnipeg, Manitoba.
Hunter syndrome, or mucopolysaccharidosis II (MPS II), is a serious genetic disorder that primarily affects males. It interferes with the body’s ability to break down and recycle specific mucopolysaccharides, also known as glycosaminoglycans or GAG. Hunter syndrome is one of several related lysosomal storage diseases.
In Hunter syndrome, GAG builds up in cells throughout the body due to a deficiency or absence of the enzyme iduronate-2-sulfatase (I2S).This buildup interferes with the way certain cells and organs in the body function and leads to a number of serious symptoms. As the buildup of GAG continues throughout the cells of the body, signs of Hunter syndrome become more visible. Physical manifestations for some people with Hunter syndrome include distinct facial features, a large head, and an enlarged abdomen. People with Hunter syndrome may also experience hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen. Range of motion and mobility may also be affected. In some cases of Hunter syndrome, central nervous system involvement leads to developmental delays and nervous system problems. Not all people with Hunter syndrome are affected by the disease in exactly the same way, and the rate of symptom progression varies widely. However, Hunter syndrome is always severe, progressive, and life-limiting.
The visible signs and symptoms of Hunter syndrome (MPS II) in younger people are usually the first clues leading to a diagnosis. In general, the time of diagnosis usually occurs from about 2 to 4 years of age. Doctors may use laboratory tests to provide additional evidence that an MPS disorder is present, before making a definitive diagnosis by measuring the iduronate-2-sulfatase (I2S) enzyme activity. The most commonly used laboratory screening test for an MPS disorder is a urine test for GAG. It is important to note that the urine test for GAG can occasionally be normal and yet the child still may have an MPS disorder. A definitive diagnosis of Hunter syndrome is made by measuring I2S activity in serum, white blood cells, or fibroblasts from skin biopsy. In some people with Hunter syndrome, analysis of the I2S gene can determine clinical severity. Prenatal diagnosis is routinely available by measuring I2S enzymatic activity in amniotic fluid or in chorionic villus tissue.
Since Hunter syndrome is an inherited disorder (X-linked recessive) that primarily affects males, it is passed down from one generation to the next in a specific way. Nearly every cell in the human body has 46 chromosomes, with 23 derived from each parent. The I2S gene is located on the X chromosome. Females have two X chromosomes, one inherited from each parent, whereas males have one X chromosome that they inherit from their mother and one Y chromosome that they inherit from their father. If a male has an abnormal copy of the I2S gene, he will develop Hunter syndrome. A male can obtain an abnormal copy of the I2S gene in one of two ways. His mother is often a carrier; i.e., she has one abnormal and one normal I2S gene, and she passes along the abnormal gene to him. However, during egg and sperm formation, a mutation can develop in the I2S gene on his X chromosome. In this second case, the mother is not a carrier and the risk of a spontaneous mutation occurring again in a future sibling is low but not zero. Females can carry one abnormal copy of the I2S gene and are usually not affected.
The human body depends on a vast array of biochemical reactions to support critical functions, including the production of energy, growth and development, communication within the body, and protection from infection. Another critical function is the breakdown of large biomolecules, which is the underlying problem in Hunter syndrome (MPS II) and related storage disorders. The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue of the body known as the extracellular matrix. This matrix is made up of a variety of sugars and proteins and helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a complex molecule called a proteoglycan. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides, otherwise known as GAG. There are several types of GAG, each found in certain characteristic places in the body
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