What to Know About Hunter Syndrome (MPS II)

Hunter syndrome aka mucopolysaccharidosis type II (MPS II) is a rare genetic disorder. It is caused by an enzyme deficiency that prevents the proper breakdown of long sugar chain molecules called glycosaminoglycans (formerly called mucopolysaccharides). Symptoms may not be obvious from birth, but the buildup of sugar molecules over time causes notable damage in organs and tissues, affecting a child’s mental and physical development. Hunter syndrome may also be called iduronate 2-sulfatase deficiency (I2S deficiency). Hunter syndrome affects more boys than girls on average. 

This article will explain Hunter syndrome including who gets Hunter syndrome, what causes Hunter syndrome, the signs and symptoms of Hunter syndrome to watch for, how it is diagnosed, and what treatment for Hunter syndrome.

What Is Hunter Syndrome?

Hunter syndrome is when someone is born with a specific digestive enzyme deficiency called lysosomal enzyme iduronate-2-sulfatase deficiency. Hunter syndrome prevents the breakdown of sugars leading to the buildup of complex sugars called glycosaminoglycans (GAGs). This sugar buildup has adverse health effects as a child develops mentally and physically.

Who Gets Hunter Syndrome?

Children get Hunter syndrome from their biological mother's DNA. Male babies have one X chromosome, and so a single copy of the IDS gene variation in each cell is enough to cause disease. Female babies, on the other hand, have two X chromosomes. This means the variation must be on both X chromosomes to cause Hunter syndrome.

What Causes Hunter Syndrome?

Hunter syndrome is caused by a genetic variation on the IDS gene located on the X chromosome and responsible for producing the lysosomal enzyme or protein called iduronate sulfatase (iduronate-2-sulfatase). Without this enzyme, proper sugar breakdown cannot occur. This leads to signs and symptoms and health complications.

Hunter Syndrome Signs and Symptoms

Signs and symptoms for Hunter syndrome vary from mild to severe, with most children experiencing a few mild symptoms. Other children may experience severe and sudden onset symptoms with serious complications. The varying degree of symptoms exists even within a single family where two children from the same genetic line can experience very different symptoms. Early onset signs of severe Hunter syndrome will start presenting around the age of two.

Early severe symptoms include:

• Aggressive and hyperactive behavior
• Decline in mental functioning 
• Intellectual disability
• Jerky body movements 
• Clouding of the front part of the eye (corneal clouding)
• Recurring upper respiratory infections, including chronic runny nose
• Enlarged or swollen tonsils and/or adenoids
• Frequent ear infections and hearing loss
• Larger than average head
• Lips and cheek thickening

How Is Hunter Syndrome Diagnosed?

There are tests available to help a healthcare provider diagnose Hunter syndrome. Tests for Hunter syndrome can include:

• Enzyme testing for sulfatase enzyme deficiency in blood serum or cells
• Genetic testing for iduronate sulfatase gene variations 
• Urine testing for signs of heparan sulfate and dermatan sulfate

A healthcare provider may also conduct a physical exam or refer someone to the appropriate specialists to look for the following signs of Hunter syndrome:

• Retina differences (i.e., structural variations in the back of the eye)
• Heart murmur or leaky heart valves
• Enlarged liver or spleen
• Groin hernia
• Joint stiffness and related symptoms
• Enlarged head and short stature

How Is Hunter Syndrome Treated?

Early intervention is crucial to prevent damage caused by Hunter syndrome. Fortunately, there are infusion or IV-treatments available for someone with Hunter syndrome. These treatments will include an interdisciplinary team of specialists in genetics, cardiology, neurology, pulmonary, and more.

Enzyme Replacement Therapy

The most likely treatment route is enzyme replacement therapy or ERT. This therapy is IV-administered and introduces the enzyme into the child’s blood stream so they can begin breaking down sugar and prevent complex sugar buildup. 

Hematopoietic Stem Cell Transplantation

Another treatment option is a hematopoietic stem cell transplantation (HSCT). In this procedure, stem cells with red and white blood cells that make our immune systems are taken from a person without Hunter syndrome and are given to the child with Hunter syndrome using intravenous technology. A type of chemotherapy not used in cancer treatments may be necessary to prepare the body for successful HSCT. Talk to your child’s healthcare team about next steps.

Complications Associated With Hunter Syndrome

Complications associated with Hunter syndrome can be considered as late onset symptoms that also get progressively worse with time.

Complications of Hunter syndrome that develop over time may include:

• Coarse or distinctly defined facial features
• Deep, hoarse voice
• Carpal tunnel syndrome
• Worsening hearing impairment leading to eventual deafness 
• Increased hair growth 
• Joint stiffness
• Distinct, white skin growth
• Ventricular hypertrophy or heart chambers enlargement 
• Hepatosplenomegaly or liver and spleen enlargement
• Hydrocephalus (fluid buildup around brain)
• Spinal cord compression 
  
• Skeletal or joint abnormalities
• Airway obstruction
• Further intellectual and mental functioning decline

Can Hunter Syndrome Be Prevented?

If you have a family history of Hunter syndrome, or if your sexual partner has a family history of Hunter syndrome, genetic counseling is recommended and prenatal testing is available. It’s also possible to get carrier testing for female relatives of affected males.

What’s the Outlook for People With Hunter Syndrome?

People with Hunter syndrome have a notably shorter lifespan than people without Hunter syndrome. People with early-onset (severe) Hunter syndrome have a lifespan of 10 to 20 years. People with the late-onset (mild) form are expected to live anywhere from 20 to 60 years.

When Can My Child Return to Regular Activities?

Hunter syndrome affects every child differently. While some children will be able to engage in regular everyday activities, others may need modifications, or additional supports in place. 

When to Call a Healthcare Provider

If you know you are a genetic carrier and you are considering becoming pregnant or having biological children, it’s also time to talk to your healthcare provider for more information specific to you and your genetic family history. 

If you’re wondering if you or your child may have Hunter syndrome based on the groups of symptoms provided in this article, including noticing developmental delays in your child, it’s time to talk to a healthcare provider. 

Summary

Hunter syndrome is a rare, inherited genetic disorder affecting how the body processes sugar. It affects more males than females as it is passed down on the X chromosome. Symptoms vary from mild to severe and include buildup of complex sugars leading to possible organ tissue damage. Treatments include enzyme replacement therapy or infusions and will be necessary for the rest of the child’s life.

Early intervention can help prevent complications such as enlarged liver and spleen. People with Hunter syndrome have a shorter lifespan on average, but this also varies greatly. If you think you or your child may have Hunter syndrome, or if you’re considering getting pregnant with Hunter syndrome, consult your healthcare provider.