Deafblind Fact Sheet: Hunter Syndrome

What is Hunter Syndrome?

Hunter syndrome, or mucopolysaccharidosis II (MPS II), is a  genetic disorder that primarily affects males. It interferes with the body's ability to break down and recyle specific mucopolysaccarides  (mew-ko-pol-ee-sak-ah-rides), also known as glycosaminoglycans (gli-ko-sah-mee-no-gli-cans) or GAG. Hunter syndrome is one of several related lysosomal storage diseases.

In Hunter syndrome, GAG build up in cells throughout the body due to a deficiency or absence of the enzyme iduronate-2-sulfatase (I2S). This buildup interferes with the way certain cells and organs in the body function and leads to a number of serious symptoms.

What are the Symptoms of Hunter Syndrome?

The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth, but usually start to become noticeable after the first year of life. 

Common early symptoms of Hunter syndrome may include:

• umbilical or inguinal hernia
• ear infections
• runny nose
• colds

Since these symptoms are quite common among all infants, they are not likely to lead a doctor to make a diagnosis of Hunter syndrome right away.  As the build up of GAG continues throughout the cells of the body, signs of Hunter syndrome become more visible and include:

• a distinctive coarseness in facial features including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue
• a large head
• an enlarged abdomen
• pebbly, ivory-colored skin lesions on upper arms, legs, and upper back
• frequent ear infections (conductive hearing loss)
• poor peripheral vision / vision loss due to build up of spinal fluid
• progressive sensorineural hearing loss
• respiratory infections / limited lung capacity
• cardiac/problems with heart valves
• epilepsy (seizure disorder)
• breathing problems while sleeping / disorganized sleep patterns
• joint of fingers, arms, and legs held in partial flexion carpel tunnel syndrome / motor fatigue
• short stature, dysplasia, and joint stiffness
• developmental delays

The rate and progression of the symptoms may be different for each person with Hunter syndrome and there is a broad range in the type and severity of the symptoms.

What is the Biochemistry of Hunter Syndrome?

The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue of the body known as the extracellular matrix. This matrix is made up of a variety of sugars and proteins and helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a complex molecule called a proteoglycan. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides, otherwise known as GAG.

In Hunter syndrome, the problem concerns the breakdown of two GAG: dermatan sulfate and heparan sulfate. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme I2S. In people with Hunter syndrome, this enzyme is either partially or completely inactive. As a result, GAG build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. As this buildup continues, it interferes with the way certain cells and organs in the body function and leads to a number of serious symptoms. The rate of GAG buildup is not the same for all people with Hunter syndrome, resulting in a wide spectrum of medical problems

What are the Genetics of Hunter Syndrome?

Hunter syndrome (MPS II) affects a calculated estimate of approximately 1 in 155,000 live male births. Since Hunter syndrome is an inherited disorder (X-linked recessive) that primarily affects males, it is passed down from one generation to the next in a specific way. Nearly every cell in the human body has 46 chromosomes, with 23 derived from each parent. The I2S gene is located on the X chromosome. Females have two X chromosomes, one inherited from each parent, whereas males have one X chromosome that they inherit from their mother and one Y chromosome that they inherit from their father.

If a male has an abnormal copy of the I2S gene, he will develop Hunter syndrome. A male can obtain an abnormal copy of the I2S gene in one of two ways. His mother is often a carrier; i.e., she has one abnormal and one normal I2S gene, and she passes along the abnormal gene to him. However, during egg and sperm formation, a mutation can develop in the I2S gene on his X chromosome. In this second case, the mother is not a carrier and the risk of a spontaneous mutation occurring again in a future sibling is low but not zero. Females can carry one abnormal copy of the I2S gene and are usually not affected. Hunter syndrome has been reported to occur in females.

How is Hunter syndrome Diagnosed?

Many of the early signs and symptoms of Hunter syndrome are commonly seen in infants and toddlers, so the road to diagnosis often takes time. The path to diagnosis often includes:

• Symptoms usually appear between 2 to 4 years of age
• Visible signs and symptoms of Hunter syndrome (MPS II) are usually the first clues
• Doctors may use libratory testing, to provide additional evidence that an MPS disorder is present and refer parents to a medical geneticist for further testing
• A definitive diagnosis of Hunter syndrome is made by measuring the iduronate-2 sufatase (12S) enzyme activity through a blood test. 

What are Needed Treatment and Supports for Hunter syndrome?

The child will need to be in the ongoing care of medical practitioners to address respiratory, pain management, eye care, and orthopedic needs.  Audiology evaluations should be completed on a regular basis to ensure that the child receives possibly needed hearing aids and/or listening devices.  The educational team may require the services of a teacher trained in the area of visual impairment and/or a teacher trained in deafness.  In the event of a combined vision and hearing loss, the child will benefit from educational techniques specific to deafblindness.  The child may require specialized instruction, aids, and/or equipment  and appropriate related services to assure access to the general education curriculum.

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