Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is a rare lysosomal storage disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulphatase (IDS or I2S). The condition, which results from sequence variants or genomic alterations in the IDS gene (IDS), is characterized by an accumulation of glycosaminoglycans (GAGs), specifically, dermatan sulfate and heparan sulfate, in the tissues of affected individuals. Consequently, patients with Hunter syndrome may have skeletal abnormalities, hernias, joint stiffness or contractures, significant airway obstruction, enlargement of the spleen and liver, valvular heart disease, hearing loss, and hydrocephalus. In addition, patients develop short stature and coarsening of the facial features, with a broad nose and nasal bridge, rounded cheeks, and thick lips. Severely affected patients also demonstrate cognitive impairment and progressive neurological regression, while patients with the mild or attenuated form may have normal intelligence or only mild delays. Children with Hunter
syndrome typically appear normal at birth but begin demonstrating symptoms of the disease in the first 18 months to 4 years of life. The lifespan of an individual with Hunter syndrome is significantly shortened. Patients with the attenuated form of Hunter syndrome (without significant cognitive deficits) may survive into adulthood, while death typically occurs in the second decade for those with the more severe form of the disease (with cognitive impairment and neurological decline). The reference standard for the diagnosis of Hunter syndrome is the demonstration of low or absent levels of IDS enzyme activity in leukocytes, lymphocytes, or fibroblasts, in an individual who exhibits features of the disorder. Since Hunter syndrome is inherited in an X-linked recessive manner, nearly all affected individuals are males, although affected females have been reported. The prevalence of Hunter syndrome is estimated to be 1 in 72,000 to 1 in 170,000 live male births. The majority of Hunter syndrome patients have the condition as the result of a deleterious sequence
variant in the IDS gene, which is located on the X chromosome at band q28. However, it is estimated that up to 20% of patients carry a large genomic rearrangement involving the IDS gene, such as a partial or whole gene deletion or an inversion between the IDS gene and a closely located pseudogene (IDS2). In the past, treatment for Hunter syndrome was primarily supportive in nature. However, enzyme replacement therapy (ERT) using the recombinant IDS enzyme idursulfase (Elaprase®; Shire Human Genetic Therapies Inc.) is now available and may improve the non-neurological manifestations of the condition.