Biochemistry of Hunter Syndrome

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 GAGs.

There are several types of GAGs, each found in certain characteristic places in the body:

GAG Location in body
Hyaluronic acid Various connective tissues, skin, cartilage, synovial fluid
Chondroitin sulfate Cartilage, cornea, bone, skin, arteries
Dermatan sulfate Skin, blood vessels, heart, heart valves
Heparan sulfate Lung, arteries, cell surfaces
Heparin Certain immune system cells
Keratan sulfate Cartilage, cornea, intervertebral discs

In Hunter syndrome, the problem concerns the breakdown of two GAGs: dermatan sulfate and heparan sulfate. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme I2S. In people with Hunter syndrome, this enzyme is either absent or deficient. As a result, GAGs build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. As this buildup continues, it interferes with the way certain cells and organs in the body function and leads to a number of serious symptoms.