What Is MPS 2?

Mucopolysaccharidosis 2 (mew-ko-pol-ee-sak-ah-ride-osis).

Mucopolysaccharidosis TYPE II (MPS II) is a serious genetic disorder that primarily affects males. It is one of several related lysosomal storagediseases. MPS interferes with the body’s ability to break down and recycle specific mucopolysaccharides (mew-ko-pol-ee-sak-ah-rides).

MPS II is one of the mucopolysaccharide diseases and is also known as Hunter Syndrome. It name derives from Charles Hunter, a professor of medicine in Manitoba, Canada, who first described two brothers with the disease in the early 1900’s.

Mucopolysaccharidosis type II (MPS II) is an inherited condition that severely affects many different parts of the body. It is considered a lysosomal storage disorder because boys with MPS II/ Hunters have lysosomes that cannot break down certain types of complex sugars. Structures called lysosomes are the recycling centers within our cells. Lysosomes contain enzymes that help our cells breakdown and reuse certain materials from the foods we eat.

Mucopolysaccharides are long chains of sugar molecule used in the building of connective tissues in the body.

“saccharide” is a general term for a sugar molecule (think of saccharin)

“poly” means many

“muco” refers to the thick jelly-like consistency of the molecules

There is a continuous process in the body of replacing used materials and breaking them down for disposal. Children with MPS II are missing an enzyme called iduronate sulfatase, which is essential in cutting up the mucopolysaccharides called dermatan and heparan sulphate. The incomplete broken down mucopolysaccharides remain stored in cells in the body causing progressive damage.

One of these important recycling enzymes is called iduronate 2-sulfatase (I2S). Hunter Patients are missing or making non-working copies of I2S enzymes. The failure of the body’s ability to break down these large sugar molecules called glycosaminoglycans (GAGs) causes undigested sugar molecules (GAGs) and other harmful substances to build up in cells throughout the body, resulting in the eventual damage or destruction to almost every system of the body.

There is no cure for Hunter Syndrome or any of the MPS diseases.

Though treatment may improve the length and quality of life for children with MPS II, those affected with the severe form often die before reaching their mid-teens from heart disease, airway obstruction, or severe neurological damage.

EFFECTS OF HUNTERS

Clinically speaking, Hunter syndrome is inherited as an X-linked recessive disorder. History shows that the effects of this disease take a devastating toll on the child’s developmental and cognitive ability to live a fruitful, healthy life. Sadly enough, children diagnosed with most severe cases of Hunter’s syndrome, represent more than two-thirds of all reported cases.

The onsets of Hunter’s symptoms are usually seen between 2 and 4 years of age. It is difficult to detect MPS2 because most symptoms are that of common childhood sicknesses. Most diagnoses come from the signs of developmental delay as children begin school. Unfortunately, it is the extensive rapid neurological degeneration that precedes and ultimately causes death in children with the severe form of Hunter syndrome.

Children with severe Hunter’s syndrome have multiple unexplained health issues. These include short stature, skeletal deformities, spine deterioration, joint stiffness, coarse/puffy facial features, developmental delays, mental retardation, unexpected seizures, premature brain failure, respiratory system problems, heart disease, carpal tunnel syndrome, the inability to walk and recognize their surroundings usually before the age of 12, and loss of life by 15.

MPS2 also has a tendency to attack and enlarge the internal organs, mainly the liver and spleen which can interfere with eating and breathing.

Potty training is a neurological function affected by MPS2/ Hunters, so training is almost impossible. As a consequence of the nervous system failure, some boys experience loose stool or chronic diarrhea. The inability to be trained is embarrassing, for the boys, frustrating, for both child and parents, and extremely costly.

Boys trying to cope with the issues of stomach extension usually have a hard time wearing properly fitting clothes. It becomes increasingly difficult to find elastic waist pants as children grow out of the toddler stage. Most articles of clothing need to be altered.

The continued storage of GAG in cells can lead to organs being affected in important ways.

The thickening of the heart valves along with the walls of the heart can result in a progressive decline in cardiac function.
The walls of the airway may become thickened as well, leading to breathing problems while sleeping (obstructive airway disease). People with Hunter syndrome may also have limited lung capacity due to pulmonary involvement.
As the liver and spleen grow larger with time, the belly may become distended, making hernias more noticeable.
All major joints (including the wrists, elbows, shoulders, hips, and knees) may be affected by Hunter syndrome, leading to joint stiffness and limited motion. Progressive involvement of the finger and thumb joints results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make it increasingly difficult to walk normally.
If carpal tunnel syndrome develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature.
In addition, pebbly, ivory-colored skin lesions may be found on the upper arms and legs and upper back of some people with Hunter syndrome. The presence or absence of the skin lesions is not helpful, however, in predicting clinical severity in Hunter syndrome.
Finally, the storage of GAG in the brain can lead to delayed development with subsequent mental retardation.

Sadly enough … the devastating effects of the disease will take control over their little lives which usually result in their passing between 10 and 15 years of age.

CAUSES OF MPS

Hunters/MPS II is an X-linked recessive condition. This means a male must inherit one copy of the non-working gene from his mother to have the condition. Although rare, females have been diagnosed with MPS II. A female must inherit two copies of the non-working gene, one from each parent, in order to have the condition. In X-linked conditions, the gene is carried on the X sex chromosome, and the condition generally affects males. While having a child with MPS II is rare, when one or both parents carry the non-working gene for the condition, they can have more than one child with the condition.

SIGNS & SYMPTOMS

The age of onset and severity of Mucopolysaccharidosis type II (MPS II) differ depending on the form. Signs of severe MPS II usually begin between ages two and four.

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.

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 buildup of GAG continues throughout the cells of the body, signs of Hunter syndrome become more visible.

Common childhood occurrences BUT early symptoms of Hunter syndrome:

inguinal hernia (Jason had this surgery at 9 weeks old)
ear infections (Jason & Justin has more than I can count, Jason had tubes put in his ears at 2 years old)
runny nose (Jason & Justin had a runny nose EVERY day from about 1 year old)
difficulty breathing (Jason & Justin were both in NICU for 5-7 days with respiratory issues at birth and then spent years at ENT appointments, Jason had his adenoids removed at 2 years old)
heart murmur (Jason was sent to a pediatric cardiologist at 3 months old with a murmur detected)

MPS II has a wide range of symptoms that vary in severity.

Jason and/or Justin Have

a distinctive coarse (puffy) facial features (full lips, large rounded cheeks, broad nose, enlarged tongue)
Large head (macrocephaly)
Enlarged/Swollen abdomen (due to enlarged liver and spleen)
Soft out-pouching around belly-button (umbilical hernia) or lower abdomen (inguinal hernia)
breathing problems while sleeping
limited lung capacity
Short pauses in breathing during sleep (sleep apnea)
Frequent upper respiratory infections
Frequent ear infections
Enlargement of vocal cords causing a deep, hoarse voice
cardiac/vascular heart disease
Hearing loss
Speech loss
Poor vision
Delayed or inability to potty train
Pebble-like white growths on the back and upper arms
Short stature
Joint stiffness (contractures) limited range of motion
carpel tunnel syndrome
Severe intellectual disability
developmental delays
Loss of basic skills, functions, and intelligence (developmental regression)
Seizures
Fluid on the brain

Physical appearances of many children with Hunter syndrome include a distinctive coarseness in their facial features (full lips & large rounded cheeks), including a prominent forehead, a nose with a flattened bridge, and an enlarged tongue. For this reason, unrelated children with Hunter syndrome often look alike.

TREATING HUNTERS

There is no cure for MPS diseases, but there are ways of managing and treating the problems they cause, including enzyme replacement therapies.

Treatments such as enzyme replacement therapies, ERT, (in our house it’s called MUSCLE JUICE) help make the disease more manageable for the body. On July 24, 2006, the FDA granted marketing approval for ELAPRASE (idursulfase), the first FDA approved enzyme replacement therapy for the treatment for MPS II, also known as Hunter syndrome.

ELAPRASE infusion therapy is administered to aid the rapid deterioration of the bodies of MPS II patients and maintain their current health conditions.

This treatment aims to supplement the enzymes that are present at low levels in the body.

Enzyme replacement therapy (ERT) can be an effective treatment for symptoms of MPS II that do not involve the skeletal system and the central nervous system (the brain and spinal cord).

Elaprase (idursulfase) is the first prescription medication prescribed for the treatment of Hunter syndrome. Elaprase is a new molecular entity, which is an active ingredient never before marketed in the United States. Elaprase was designated as an orphan product by the FDA. Orphan products, such as Elaprase, are generally developed to treat rare diseases or conditions that affect fewer than 200,000 people in the United States. Hunter Syndrome is so rare, there are less than 350 known cases that are being treated in the United States today, less than 10 live in New Jersey.

What is ELAPRASE?

ELAPRASE is an enzyme replacement therapy from Shire Human Genetic Therapies. ELAPRASE is designed to replace iduronate-2-sulfatase (I2S), the enzyme that is deficient or absent in people with Hunter syndrome (Mucopolysaccharidoses-2) Unfortunately, ELAPRASE is a weekly lifelong infusion therapy, which means it is given intravenously (by IV) over a 4-hour span.

Some patients experience some types of allergic reactions to ELAPRASE (idursulfase) infusion, but doctors can help patients with these reactions by pre-medicating, or administering medication at the time of reaction. (Jason was one of them). Patients with compromised respiratory function or acute respiratory disease may have a higher risk of a life-threatening reaction to ELAPRASE infusion and require additional monitoring throughout the infusion.

ELAPRASE Enzyme Replacement Therapy is considered one of the World’s Most Expensive medical treatments out today, with an estimated cost reaching approximately $300,000 – $500,000per patient, per year, depending upon the plan participant’s weight.

The average wholesale price (AWP) of a single-use vial of ELAPRASE is $3,285.00. For each patient, this results in a projected cost of approximately $6,570.00 per week, per child.

For more information on the treatment, visit http://www.elaprase.com/.

THERAPIES

Physical therapy is a very important part of treating the signs and symptoms of MPS II. Consistent physical therapy early on can help preserve mobility and lessen pain and joint stiffness. Some children also may require developmental or occupational therapy to help reach and retain milestones.

COMMON SURGERIES

As your child grows, your child’s health care provider may recommend surgeries to improve the quality of life. Removal of the tonsils and adenoids and insertion of ventilating tubes can prevent some upper respiratory infections and may reduce hearing loss. In children with attenuated to severe MPS II who develop a build-up of fluid in the brain (hydrocephaly), a surgery to relieve the pressure inside the skull may be recommended. Other surgeries would not take place until later in life, if at all. Joint replacement surgery and surgery to treat carpal tunnel syndrome can improve mobility and lessen pain. Heart valve replacement may prevent later heart complications.

DIET

A dietician can help you create a nutrition plan to help control diarrhea and constipation, which may occur in those with severe MPS II and some of the early stages of hyperactivity. There is no diet that can prevent the storage of GAGs because they are actually created by the body.