What is mucopolysaccharidosis type II?

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare inherited lysosomal storage disease in which the body is missing or does not have enough of an enzyme needed to break down long chains of sugar molecules called glycosaminoglycans (GAGs). As a result, the GAGs build up in different body systems and result in manifestations of disease.

An early-onset form of the disease begins shortly after birth and is more severe. In a late-onset form, less severe symptoms appear later in life.

Causes of mucopolysaccharidosis type II

MPS II is caused by a disease-causing (pathogenic) gene mutation in the IDS gene. This gene provides instructions for the production of the enzyme, iduronate 2-sulfatase, which works to break down GAGs. 

The affected IDS gene is on the X chromosome. As such, boys are almost exclusively affected because they inherit the X chromosome from their mothers. Their mothers do not have symptoms of the disease, but they carry a nonworking copy of the gene.

Symptoms of mucopolysaccharidosis type II

Children with MPS II often have no symptoms of the condition at birth. People with severe MPS II generally begin to show signs and symptoms of the disorder between 18 months and 4 years of age. Symptoms of slowly progressive forms of MPS II tend to present a couple of years later. Individuals with MPS II typically develop macrocephaly (large head size) and coarse facial features, such as full lips, rounded cheeks, and a broad nose. Other common manifestation of MPS II include enlargement of the liver and spleen, frequent upper respiratory infections, recurrent ear infections and hearing loss, hernias, joint stiffness and dysostosis multiplex, carpal tunnel syndrome, valvular heart disease, hydrocephalus, and GI upset. In addition, growth for children with MPS II usually slows after age 5.

Diagnosis of mucopolysaccharidosis type II

Early diagnosis is challenging because the symptoms of MPS II can also be attributed to many other more common disorders. Diagnosis is made by a physical exam and one of the following:

1. Low iduronate 2-sulfatase enzyme activity
2. Elevation of plasma and/or urine GAGs

Diagnosis can be confirmed by genetic testing, which will reveal a pathogenic variant in the IDS gene.

Treatment for mucopolysaccharidosis type II

Currently, there is no cure for MPS II, but there is treatment available.

Enzyme replacement therapy (ERT) uses an intravenous infusion to replace the deficient or missing enzyme in the body.  

Patients are followed at least regularly by the Lysosomal Storage Disease (LSD) Center at Children’s Hospital of Philadelphia (CHOP) in its multidisciplinary MPS Clinic. The clinic includes appointments with Physical Therapy and Developmental Pediatrics. Patients are also followed by other subspecialists including Pulmonology, Cardiology and Orthopedics, among others.

In addition, the Cell and Gene Therapy Collaborative at CHOP is conducting gene therapy clinical trials for MPS II, with the aim of developing new gene therapies for this disease.