Hunter Syndrome

Synonyms

3

Overview

Hunter syndrome or Mucopolysaccharidosis II (MPS II) is an inherited disorder of carbohydrate metabolism that occurs almost exclusively in males. It is characterized by distinctive facial features, a large head,  hydrocephalus, enlargement of the liver and spleen (hepatosplenomegaly), umbilical or inguinal hernia, and hearing loss. Individuals with this condition may additionally have joint deformities and heart abnormalities involving the valves. MPS II is caused by mutations in the IDS gene and is inherited in an X-linked manner.

There is a wide range in severity of symptoms present in individuals with MPS II. Previously, MPS II was classified as severe and attenuated based on severity. More recently, the terms slowly progressive and early progressive have been suggested. While both types affect many different parts of the body, people with the severe type also experience a decline in intellectual function and a more rapid disease progression. The life expectancy for people with the severe type is 10 to 20 years. Individuals with the less severe type typically live into adulthood and intelligence is not affected. Treatment is focused on managing the signs and symptoms present in each individual.

Symptoms

Hunter syndrome symptoms vary and range from mild to severe. Symptoms aren't present at birth, but often begin around ages 2 to 4.

Signs and symptoms may include:

  • An enlarged head (macrocephaly)
  • Thickening of the lips
  • A broad nose and flared nostrils
  • A protruding tongue
  • A deep, hoarse voice
  • Abnormal bone size or shape and other skeletal irregularities
  • A distended abdomen, as a result of enlarged internal organs
  • Diarrhea
  • White skin growths that resemble pebbles
  • Joint stiffness
  • Aggressive behavior
  • Stunted growth
  • Delayed development, such as late walking or talking

Causes

Hunter syndrome is an inherited condition. Boys are most often affected. The condition is caused by a lack of the enzyme iduronate sulfatase. Without this enzyme, mucopolysaccharides build up in various body tissues, causing damage.

The early-onset, severe form of the disease begins shortly after age 2. A late-onset, mild form causes less severe symptoms to appear later in life.

Prevention

Genetic counseling is recommended for couples who want to have children and who have a family history of Hunter syndrome. 
MPS II is inherited in an X-linked recessive pattern, which means that this conditions occurs almost exclusively in males. Females are generally unaffected carriers of this condition. In a family with more than one affected individual, the mother of the affected males must be a carrier. When a carrier female has a child, there is a 25% (1 in 4) chance that she will have a affected son.

Diagnosis

Babies born with Hunter syndrome almost always appear healthy at birth. Changes in facial features are often the first noticeable sign that something's not right.

Blood, urine or tissue samples can be checked for the deficient enzyme or for excess amounts of the complex sugar molecules associated with this disorder. A genetic analysis can confirm the diagnosis.

Because Hunter syndrome progresses slowly and its signs and symptoms overlap with a number of other disorders, definitive diagnosis may take some time.

Prenatal testing:
Prenatal testing of the fluid that surrounds the baby (amniocentesis) or of a tissue sample from the placenta (chorionic villus sampling) can verify if your unborn child carries a copy of the defective gene or is affected with the disorder.

Prognosis

People with the early-onset (severe) form usually live for 10 - 20 years. People with the late-onset (mild) form usually live 20 - 60 years. Complications include:

  • Airway obstruction
  • Carpal tunnel syndrome
  • Hearing loss that gets worse over time
  • Loss of ability to complete daily living activities
  • Joint stiffness that leads to contractures
  • Mental function that gets worse over time
  • Calling your health care provider

Treatment

Because of the very specific nature of the illness, treatment has been proven very difficult. The treatment for this disorder can usually be diagnosed specifically for patients because all cases are different.

Palliative treatment

Due to the nature of the illness, and absence of a really efficient treatment, it is important to emphasize the need for extensive palliative treatment against the diverse symptoms. Their objective is to reduce the effects of the deterioration of many bodily functions. In light of the diversity of symptoms, it is quite common to use a wide spectrum of palliative strategies where surgery and therapies are often pivotal.

Bone marrow transplantation

For a long time, the most efficient approach had been to use bone marrow graft, emerging into hematopoietic stem cell transplantation. Based upon the same theory, they each have the advantage of procuring a new source of the missing I2S. However, the results have been considered imperfect at best.

While this treatment alternative is able to improve or stop the progression of some of the physical symptoms, it does not prevent the eventual cognitive regression that occurs in Hunter syndrome patients who are cognitively affected, although it may slow such regression early on. Therefore, for attenuated patients, this may still serve as a viable treatment option because of its more permanent nature, possibly even equivalent to weekly enzyme replacement therapy, resulting in much improved life expectancy.

However, even for attenuated patients, it is a major intervention with not insignificant mortality risks and potential for life-threatening or altering complications such as graft-versus-host disease. For cognitively affected patients, without solving the challenge of cognitive regression, it is limited at best as a permanent treatment alternative. Because of all these reasons, grafts have seen a decrease in their application as Hunter syndrome treatment.

Approved therapies:
Idursulfase (Elaprase) - FDA-approved indication: Indicated for patients with Hunter syndrome (mucopolysaccharidosis II, MPS II). Idursulfase has been shown to improve walking capacity in these patients  

Resources

Refer to Research Publications.