Numerous biochemical reactions support key functions in the human body. These functions include energy production, communication within the body, growth, development and the fight against infection. Another important function is the breakdown of large biomolecules. A fault in the breakdown of these molecules is the pathological mechanism behind hunter syndrome and other storage diseases.
Hunter syndrome is a lysosomal storage disease caused by a either a deficiency or complete absence of the enzyme iduronate-2-sulfatase (I2S). This enzyme is usually responsible for the breakdown of glycosaminoglycans (GAGs). The biochemistry of this syndrome concerns a problem that occurs in the extracellular matrix, which makes up part of the body’s connective tissue.
This extracellular matrix is composed of different sugars and provides an organized meshwork that surrounds all cells of the body. It acts as a glue in which the cells are suspended and held together. One important molecule that makes up the extracellular matrix is proteoglycan. This complex molecule needs to be broken down and replaced and one of the products that results form this process is GAG.
There are several types of GAG in the body and in hunter syndrome it is the GAGs dermatan sulfate and heparan sulfate that fail to be broken down. The first step in the breakdown of dermatan sulfate and heparan sulphate is mediated by the I2S enzyme. However, deficiency or absence of this enzyme in people with Hunter syndrome means GAG accumulates in cells throughout the body, particularly in tissues where dermatan sulfate and heparan sulfate are abundant.
As increasing amounts of GAGs collect in the cells, the function of organs and cells is increasingly compromised, leading to more severe symptoms as the disease progresses. The rate of GAG accumulation varies between individuals, meaning a wide spectrum of symptoms and complications are observed in Hunter syndrome.
Reviewed by Sally Robertson, BSc