Mucopolysaccharidosis II (MPS II)
MPS II, also called Hunter syndrome, is caused by a deficiency of an enzyme (iduronate sulfatase) that is needed to break down the mucopolysaccharides/glycosaminoglycans (GAGs) dermatan and heparan sulfate, which are found in the central nervous system and throughout other systems of the body. GAGs are long, repeating chains of complex sugar molecules. When the enzyme is absent, a progressive buildup of the GAG material occurs in many of the tissues of the body and leads to many health problems.
Forms of the disorder
Hunter syndrome is traditionally divided into severe and mild forms. However, the clinical symptoms may be highly variable. The frequency of Hunter syndrome is estimated at 1 in every 100,000 to 150,000 births.
Clinical features
Individuals with severe Hunter syndrome usually begin to display symptoms by 18 to 36 months of age. These symptoms may include joint stiffness, “claw-like” hands, short stature, coarse facial features (flattened nose bridge, thick lips and an enlarged tongue), an enlarged liver and spleen, hernias, hearing loss, chronic nasal discharge and congestion and developmental delay. The symptoms may be very similar to those seen in Hurler syndrome (MPS IH) except that there is no corneal clouding.
Individuals with mild Hunter syndrome may not be diagnosed until school-age, adolescence or adulthood. Mildly affected individuals may experience many of the same physical symptoms seen in the severe form, except that these symptoms are milder in nature. Typically, intelligence is not affected in the mild form of the disorder.
Genetics of the disorder
MPS II is inherited as an X-linked (sex-linked) recessive trait, meaning that it is usually observed only in males. Males have one X chromosome paired with a Y chromosome and females have two X chromosomes. If a male has a recessive gene for MPS II on his only X chromosome, he will have the condition because he has no matching gene to cancel it out on the Y chromosome.
In females, because they have two X chromosomes, an X chromosome with a normal gene can mask the effect of the altered gene on the other X chromosome. In these instances, the female would be referred to as a carrier for the condition. If a female is a carrier for MPS II, there is a 50% chance that a son would have the condition. Likewise, there is a 50% chance that any daughter would be a carrier for the condition. In rare cases, a son may develop MPS II not because his mother is a carrier, but due to a new mutation or change in the gene. This possibility can be addressed through genetic testing.
Treatment
Despite the fact that there is no cure for MPS II, therapies do exist to treat the symptoms of the disorder. A new method of treatment for MPS II is enzyme replacement therapy (ERT). Management of the disorder also involves symptomatic treatment of specific complications that can arise.
Registry
The Hunter Outcome Survey (HOS) is an ongoing, strictly observational study that records the natural history and outcomes of patients with MPS II. There is no experimental intervention involved. The purpose of this registry is to collect clinical information on a large number of patients throughout the course of their lives. The survey is a way for healthcare professionals to share information in a manner that respects patient confidentiality, but at the same time contributes to a greater understanding of the disorder and serves as a tool in the ongoing search for a cure for MPS II.