What are the other Names for this Condition? (Also Known as/Synonyms)

• Hunter Syndrome
• I2S (Iduronate 2-Sulfatase) Deficiency
• Iduronate 2-Sulfatase (I2S) Deficiency

What is Mucopolysaccharidosis Type II? (Definition/Background Information)

• Mucopolysaccharidosis Type II (MPS II) is a genetic disease caused by deficiency of an enzyme that is responsible for breaking-down large molecules, called glycosaminoglycans, within cells
• When the cells cannot digest the large molecules, they accumulate. Eventually, the patient’s cells are overwhelmed by their own molecular “garbage” and unable to function properly, leading to MPS II signs and symptoms
• The disease affects many different parts of the body. The severity of the condition varies, but the symptoms get progressively worse over time
• Often symptomatic treatment and therapeutic support is provided for MPS II. However, the prognosis of the condition is poor

Who gets Mucopolysaccharidosis Type II? (Age and Sex Distribution)

• Mucopolysaccharidosis Type II is an inherited genetic condition that occurs almost exclusively in males. Approximately, 1 in every 100,000 to 170,000 males are affected
• Among the Jewish population (in Israel), the incidence of MPS II is observed at a much higher rate; up to 1 in 34,000 males are affected

What are the Risk Factors for Mucopolysaccharidosis Type II? (Predisposing Factors)

The risks of Mucopolysaccharidosis Type II include the following factors:

• Deficiency of iduronate 2-sulfatase, an enzyme necessary to breakdown heparin sulfate and dermatan sulfate (both are types of carbohydrates), in cell lysosome
• Genetic factors: MPS II is an X-linked autosomal recessive condition, and hence male children are always affected. The mothers of the affected male children carry the disease gene, without having the disease themselves
• Having a positive family history of the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mucopolysaccharidosis Type II? (Etiology)

• Mucopolysaccharidosis Type II genetic disorder is caused by mutations in the IDS gene. The gene encodes an enzyme, iduronate 2-sulfate (I2S), which breaks down complex molecules, called glycosaminoglycans (GAGs)
• Different mutations of the IDS gene can lead to either partially functioning I2S enzyme, or to a complete loss of the enzyme function. A complete loss of the enzyme function leads to a more severe, rapidly progressing disease. Hence, MPS II is also known as Iduronate 2-Sulfatase Deficiency disorder
• The IDS gene is inherited in an X-linked recessive pattern. Normally, males have only one X chromosome that is inherited from their mothers. If that chromosome has a mutant IDS gene, then the male can be affected by MPS II. In contrast, females have two X chromosomes, one from each parent. If one X chromosome has a mutated IDS gene, the  other normal X chromosome is able to make up for this defect, because it encodes normal enzymes, and cells are able to function with only one “good” IDS gene. So, females are almost never affected by the genetic condition. However, they can pass the defective gene onto their offspring
• Complex molecules glycosaminoglycans used to be called “mucopolysaccharides”, and the term “mucopolysaccharidosis” literally means an overabundance of mucopolysaccharides. The disease is also a kind of “lysosomal storage disease”, because (when not broken down) glycosaminoglycans accumulate within special compartments of the cells, called lysosomes
• Lysosomes are a kind of recycling plant within the cells - they break down larger, more complex organic molecules into smaller molecules, which the cells can then reuse. When important enzymes, like I2S, are not functioning efficiently, the lysosomes become bloated and eventually, the cell gets ‘filled-up’ being unable to function anymore, leading to a disease condition

What are the Signs and Symptoms of Mucopolysaccharidosis Type II?

The signs and symptoms of Mucopolysaccharidosis Type II genetic disorder are numerous, affecting multiple body parts and organs. These include the following:

• The earliest symptoms start at ages 2-4 years, primarily affecting the head and neck. The lips, tongue, and vocal cords enlarge, resulting in a deep, hoarse voice. The nose and facial features become more broad and full
• Frequent upper respiratory infections and sleep apnea (difficulty breathing while sleeping) may be observed. Problems with breathing may require medical assistance
• Enlarged heart, possibly leading to heart valve abnormalities and heart failure
• Enlargement of the head, liver, and spleen
• Umbilical or inguinal hernia
• Recurrent ear infections and/or hearing loss
• Multiple skeletal and joint deformities, starting around age 5 years
• Children have a short stature
• Carpal tunnel syndrome (as a child) and spinal stenosis may be observed
• Sometimes, reduced vision (retinopathy)
• A distinctive skin condition with white, pebble-like growths may be noticed

How is Mucopolysaccharidosis Type II Diagnosed?

The diagnosis of Mucopolysaccharidosis Type II may include the following tools:

• Physical exam with evaluation of medical history, including family history
• Radiographic studies for overall skeletal survey/picture, such as using CT or MRI scans
• Urine and blood analysis, ELISA test
• Prenatal exams, which may include amniocentesis and chorionic villus sampling
• Evaluation of airways, hearing, eyesight
• ECG and cardiac echocardiography
• Genetic tests and analysis is needed for a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mucopolysaccharidosis Type II?

Complications due to Mucopolysaccharidosis Type II could include:

• Deafness in children
• Degenerative disease affecting the joints, especially the hips; occurs in slightly older individuals
• Heart valve related problems, hypertension
• Neurological complications
• Obstructive airway disease, due to lung wall thickening
• Liver, spleen enlargement could progressively lead to abdominal hernia

How is Mucopolysaccharidosis Type II Treated?

Mucopolysaccharidosis Type II disorder has no known cures; it is a relentless genetic condition that progressively gets worse. An individual treatment (case-by-case approach) is provided to improve the quality of life. This is also based on the specific set of signs and symptoms and complications that develop in each child/individual.

• Some of the physical defects may be corrected and surgical procedures performed (for cardiac and other abnormalities)
• But for improving motor skills and mental disabilities, special therapeutic treatment (by speech, physical, and occupational therapists) and supportive care is required
• Recent treatment techniques that are under consideration include enzyme replacement therapy, bone marrow transplantation, and gene therapy

How can Mucopolysaccharidosis Type II be Prevented?

• Currently, there are no specific methods or guidelines to prevent Mucopolysaccharidosis Type II genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests, scans and physical examinations are very important

What is the Prognosis of Mucopolysaccharidosis Type II? (Outcomes/Resolutions)

• Mucopolysaccharidosis Type II is a fatal genetic disorder. Most children, who survive the initial few years, are severely affected by multiple congenital defects and developmental deformities
• However, with constant care and support by families and medical aids, some individuals live to adulthood and are able to manage their lives to some extent
• Some individuals with severe disease begin to lose basic functioning skills, starting at the age of 6-8 years and have significantly impaired mental function. Such individuals rarely live beyond the age of 20 years
• Airway obstruction and heart disease are the major factors that cause death in patients with MPS II

Additional and Relevant Useful Information for Mucopolysaccharidosis Type II:

There are volunteer organizations and support groups that provide help and understanding to the families and parents of those affect by Mucopolysaccharidosis Type II.