Hunter Syndrome (Mucopolysaccharidosis II, MPS II)

Abnormalities in an individual's genetic makeup cause genetic disease.

Hunter syndrome is a very rare X-linked recessive inherited disease. Hunter syndrome is a lysosomal storage disease caused by deficient or absent enzyme, iduronate-2-sulfatase (I2S). This causes the accumulation of heparin sulfate and dermatan sulfate to accumulate in body tissues. Injury to various organs leads to the symptoms of the disease. Hunter syndrome is also termed Mucopolysaccharidosis II or MPS II.

The cause of Hunter syndrome is an abnormal gene X chromosome that is inherited from the mother. This genetic abnormality allows mucopolysaccharides to accumulate in large amounts in cells, the blood, and in connective tissues. This accumulation causes damage to cells and organs. It is a progressive disease that usually causes a shortened lifespan and major developmental abnormalities. Hunter syndrome occurs almost exclusively in males.

The two major risk factors for Hunter syndrome are a family history of Hunter syndrome, and being male, since predominantly males are affected. Females rarely get the disease because they inherit two X chromosomes so that even if one is defective, the other X chromosome with functioning genes usually can compensate for the abnormality.

The symptoms of Hunter syndrome usually are not present at birth, but begin in young children ages about 2-4, and may range from mild to severe.

Symptoms of Hunter syndrome include:

• Facial changes such as thickening of the lips, nostrils flaring, and broadening of the nose
• Head enlargement (macrocephaly)
• Tongue protrusion
• Hoarseness and/or deepening of the voice
• Changes in the bones produce abnormal bone size and/or bone shape
• Joint stiffness
• Small whitish growths on the skin
• Enlarged internal organs
• Distended abdomen
• Diarrhea
• Delayed development (for example, the child does not meet normal development such as talking or normal motor skills like walking)
• Behavior that becomes aggressive
• Reduced or stunted growth

Several physician specialties may treat Hunter syndrome. Treatment is geared toward managing the symptoms and complications of the disease. There is no cure for this progressive disease.

Specialties of physicians that may be involved in caring for persons with Hunter syndrome include:

• Pediatric pulmonologists
• Critical-care specialists
• Emergency medicine specialists
• Orthopedists
• Geneticists
• Rheumatologists
• Internal medicine specialists
• Neurologists
• Surgeons
• Child psychologists

If the child survives to adulthood, similar specialists that treat adults may be consulted.

The diagnosis of Hunter syndrome is sometimes difficult because of its slow onset and overlapping symptoms with other childhood problems. Early signs that suggest a diagnosis include facial changes in the child. The pediatrician then usually completes a detailed personal family history and physical examination of the individual. Blood, urine, and/or tissue samples can be tested for either the deficient enzyme or excess mucopolysaccharides.

Definitive diagnosis is done by a genetic analysis of the child's X chromosome(s). There is no routine newborn screening available to diagnose Hunter syndrome. However, in families with known Hunter syndrome, prenatal testing of the amniotic fluid or placental tissue may be available and can verify the diagnosis in a fetus.

Currently, treatment is geared toward managing symptoms and complications as there is no cure for this progressive disease.

Treatments depend on the organ(s) involved and can include:

• Assistance with breathing
• Physical therapy to maintain functions
• Drainage of fluids to build up in the brain and/or spinal cord
• Heart valve replacement
• Other treatments such as behavior management

Some physicians utilize specific enzyme therapy to replace a child's deficient enzymes. The treatment is termed enzyme replacement therapy (ERT) using an IV–infused enzyme (Elaprase). It is still being refined along with gene therapy to replace the abnormal part of the X chromosome.

The life expectancy of the person with Hunter syndrome is reduced and ranges from about 10 to 20 years of age. However, with mild disease, some individuals live into adulthood. Obstruction of breathing or heart disease are the major causes of death.

Complications of Hunter syndrome include:

• Respiratory complications (thickened tongue can obstruct breathing)
• Skeletal problems (abnormal bone development and joint problems)
• Connective tissue (accumulation of mucopolysaccharides can cause swelling)
• Heart (thickened tissue resulting in vessel narrowing)
• Brain (hydrocephalus)
• Nervous system (thickened membranes impede nerve functions)
• Reduced ability to recover from most illnesses

Hunter syndrome is also known as the following:

• Mucopolysaccharidosis II
• MPS II
• MPS Disorder II

Some researchers use subtypes such as MPS IIA and MPS IIB (MPS IIA is a severe disease while MPS IIB is a mild disease).

Two other terms that are sometimes confused with Hunter syndrome include:

1. The first is Bow Hunter Syndrome, a problem when a person rotates their head and causes circulation ischemia in the dominant vertebral artery that produces attacks of vertigo, nystagmus, and ataxia (inability to walk normally).
2. The second term is Hurler Hunter syndrome. This term also is known as Hurler syndrome (mucopolysaccharidosis I and MPS I) and is closely related to Hunter syndrome because it also is an inherited disease that results in a lack of an enzyme called alpha-L-iduronidase, which produces similar symptoms and outcomes to Hunter syndrome.