Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The rare disease that we will be learning about today is:
Also called mucopolysaccharidosis II (MPS II), but Hunter syndrome is less of a mouthful.
What is Hunter Syndrome?
- MPS II is a mucopolysaccharide disease known as Hunter syndrome. It takes its name from Charles Hunter, the professor of medicine in Manitoba, Canada, who first described two brothers with the disease in 1917. MPS II has a wide range of symptoms that vary in severity and can be managed and treated with enzyme replacement therapies. There is no cure for MPS II.
- This is a rare condition affecting 1 in 100,000 to 1 in 170,000 people, primarily males.
- MPS II primarily occurs in males, and females may be carriers of the gene for MPS II. Although rare, MPS II has been diagnosed in females. If the mother is a carrier, there is a 50 percent chance that any male born will have the disease. The sisters and maternal aunts of a person with MPS II may be carriers of the disease and would also have a 50 percent chance of passing the syndrome to a son.
- Diagnosis requires documentation of reduced or absent iduronate 2-sulfatase enzyme activity in blood or skin cells.
- Molecular genetic testing for mutations in the IDS gene is available to confirm the diagnosis.
- Mucopolysaccharides are chains of sugar molecules used to build connective tissues in the body.
- “muco” refers to the thick jelly-like consistency of the molecules
- “poly” means many
- “saccharide” is a general term for a sugar molecule
- The body constantly replaces used materials and breaks them down for disposal. MPS II patients are missing the enzyme iduronate sulfatase, which is essential to breaking down the mucopolysaccharides dermatan and heparan sulphate. These materials remain stored in the body’s cells, causing progressive damage. Babies may show little sign of the disease, but as cells sustain damage, symptoms start to appear.
- Patients with Hunter syndrome do not produce a sufficient amount of an enzyme called iduronate-2-sulfatase.
- This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs).
- Since patients with Hunter syndrome cannot break these substances down, the GAGs gradually build up in most of the organs in the body and can damage them.
- This causes a range of disease-related signs and symptoms, including diminished lung function and decreased walking capacity.
How Do You Get It?
- MPS II is an X-linked recessive genetic condition. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome inherited by the mother and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an altered gene he will develop the disease.
- Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
What Are The Symptoms?
- In infancy, there are certain signs and symptoms that can indicate Hunter syndrome such as:
- Distinctively large facial features (full lips, large rounded cheeks, broad nose, enlarged tongue)
- Enlargement of vocal cords causing deep, hoarse voice
- Frequent upper respiratory infections
- Short pauses in breathing during sleep (sleep apnea)
- Large head (macrocephaly)
- Swollen abdomen (due to enlarged liver and spleen)
- Soft out-pouching around belly-button (umbilical hernia) or lower abdomen (inguinal hernia)
- Thick, non-stretchy skin
- Pebble-like white growths on back and upper arms
- Hearing loss
- Frequent ear infections
- Poor vision
- Short stature
- Joint stiffness
- Intellectual disability
- Developmental regressions
- The most important suggestive findings from age 18 months to 4 years are coarse facial features, enlarged spleen and liver, short stature, and joint contractures.
- Other suggestive findings pre-diagnosis include:
- sleep disturbance
- increased activity
- behavior difficulties
- Seizure-like behavior
- Perseverative chewing behavior
- Inability to achieve bowel and bladder training may be strongly correlated with subsequent cognitive dysfunction.
- A skeletal survey may show skeletal anomalies known collectively as dysostosis multiplex; however, these findings may not be present in early life and are not specific to MPS II.
- Subtle early signs and symptoms such as frequent ear/sinus infections and umbilical hernia are often present.
- Urine glycosaminoglycans (GAG) analysis shows large concentrations of the GAGs dermatan sulfate and heparan sulfate; however, these findings are not specific to MPS II as the profile is similar to that seen in MPS I.
How Is It Treated?
- There is no cure, but treatments like enzyme replacement therapies can help make the disease more manageable.
- The involvement of specialists for each affected organ system is required to monitor and treat specific problems.
- Commonly required interventions include the following:
- Shunting for hydrocephalus
- Tonsillectomy and adenoidectomy
- Positive pressure ventilation (CPAP or tracheostomy)
- Carpal tunnel release
- Cardiac valve replacement
- Inguinal hernia repair
- Hip replacement
- Developmental, occupational, and physical therapy are often necessary.
- Commonly required interventions include the following:
- The goal of treatment of patients with Hunter syndrome is vital to prolong their quality of life.
- Some treatments that are in their early stages of development have had some success by slowing the disease’s progress and lessening its severity.
- Enzyme therapy. This treatment uses man-made or genetically engineered enzymes to replace your child’s missing or defective enzymes and ease the disease symptoms.
- This treatment uses man-made or genetically engineered enzymes to replace your child’s missing or defective enzymes and ease the disease symptoms. This treatment is given once a week through an intravenous (IV) line.
- Given early enough, enzyme replacement therapy may delay or prevent some of the symptoms of Hunter syndrome. It’s unclear, however, if the improvements seen with this therapy are significant enough to raise quality of life for people with the disease. In addition, benefits in thinking and intelligence haven’t been seen with enzyme replacement therapy.
- Serious allergic reactions can occur during enzyme replacement therapy. Other possible side effects include headache, fever, skin reactions, and high blood pressure. Side effects tend to lessen over time, however.
- Examples: idursulfase
- Gene therapy. Replacing the chromosome responsible for producing the missing enzyme could theoretically cure Hunter syndrome, but much more research is needed before this therapy will be available. Trials have been under way since 2019.
- Bone marrow and stem cell transplant have been tested in some studies. The approach provides some benefit from certain organ systems, but in comparison to its use in related diseases, the results haven’t been satisfactory. This approach also fails to address the neurological problems caused by Hunter syndrome.
- In severe cases, death usually occurs by age 15. In attenuated cases, patients may survive into their 50s.
- The life expectancy of these individuals is 10 to 20 years. Individuals with mild MPS II also have a shortened lifespan, but they typically live into adulthood and their intelligence is not affected. Heart disease and airway obstruction are major causes of death in people with both types of MPS II.