Mucopolysaccharidosis Type II (IDS)
Mucopolysaccharidosis type II, also known as Hunter syndrome, is a pan-ethnic disease caused by pathogenic variants in the gene IDS. It is inherited in an X-linked manner, and therefore males are predominantly affected, although rare female carriers may manifest symptoms. This gene encodes the enzyme iduronate 2-sulfatase, which breaks down specific molecules in cell lysosomes. When this enzyme does not function properly, excess molecules are retained in the lysosomes of various cells in the body. The age of onset and severity of symptoms varies between affected males, but the most common, and severe, form is diagnosed between 2 and 4 years of age. This storage disorder results in progressive symptoms including coarsening of the facial features, skeletal dysplasia, joint contractures, excess organ size, intellectual disability and hearing loss. Growth is stunted and death occurs due to failure of the heart and lungs, usually in adolescence. Some patients have a more slowly progressing disease course, where the age of onset is later and patients may survive into adulthood or middle age. In this form, intelligence is not usually affected. Several specific variants are associated with the development of either the early or later-onset form, but many variants do not have a known genotype-phenotype correlation.
For information about carrier frequency and residual risk, please see the residual risk table.