The broken metabolism in Hunter syndrome

Understanding Hunter syndrome, a genetic metabolic disease

Figure 1: Progressive accumulation of GAGs in cells of children with Hunter syndrome

GAGs are long molecules which are present in all tissues and organs to provide support to cells. GAGs are constantly recycled; being produced and then broken down as required. I2S is able to metabolise two specific types of GAGs known as heparan sulfate and dermatan sulfate.

Dermatan sulfate: this is the major GAG in skin and is also distributed in tendons, ligaments, cartilage and other tissues.

Heparan sulfate: this is associated with supportive tissue in skin, muscle and nervous cells, in addition to the lungs, liver, brain, and aorta in the heart.

In Hunter syndrome GAGs cannot be broken down, but new GAGs continue to be made. This results in the continuous accumulation of GAGs in the lysosomes of cells. These lysosomes begin to swell, affecting cell function which in turn causes multi-organ damage with many widespread symptoms as detailed below.