Hunter Syndrome – causes, symptoms, diagnosis, treatment

Charles A. Hunter (1873-1955) is the physician who reported hunter syndrome in 1917. The name of the syndrome is after this discovery. He is the one who reports two brothers with hunter syndrome.


Hunter syndrome is an infrequent disease, it is the disorder genetically inherited from parents to offspring. The other name of hunter syndrome is mucopolysaccharidosis II or MPS II, which is transferred from one family to another. It is mostly influenced by boys. An infected person cannot break a sort of sugar which forms bones, tendons, skin, and other tissues.

That sugar increases in their cells and harms various body parts, e.g. also covers the this disorder, large molecules of sugar referred to as glycosaminoglycan or MPS II, begin to be stored in the body tissue. It is the appearance of lysosomal storage disease. Exactly what takes place in the body varies from person to person.

What are causes of Hunter Syndrome?

It is a dynamic and dangerous is the sickness of some related lysosomal storing. Hunter syndrome is caused by loss or malfunctioning of enzymes. That enzyme is known as iduronate 2-sulfatase enzyme.

The function of this enzyme is lysosome of certain large molecules such as glycosaminoglycan, but if the body does not have enough that enzyme then these large molecules which need to be broken accumulate in the body tissue and cause severe physical and mental developmental disabilities for permanent.

This occurs due to mutation in the IDS gene. This gene is given information for the formation of I2S enzyme. When mutation takes place in the IDS gene, it decreases or completely loses the I2S enzyme function. The lack of this enzyme causes the accumulation of large molecules such as glycosaminoglycan in the body parts particularly in cells of lysosomes.

The lysosome is the organelle in the cell which plays a role in the digestion and recycling of certain molecules. Large molecules such as MPS II are stored in the lysosome called the lysosomal storage disorder. It increases the size of lysosomes that is why various tissues and organs become too large.

It is believed that inside the lysosome protein functions are disrupted by GAG and disturb the movement of molecules in the cell.

Males with hunter syndrome are not able to make proteins because mutation takes place in the part of their DNA which is known as a gene. The affected part of the gene is present on x chromosomes. That is why most males are infected by hunter syndrome because they inherit the x chromosome from their mother whereas females do not have this syndrome until she receives the same infected gene from her father.

A mother does not have the disease but she carries it. It is transferred in a male from his mother. Whereas the female gets the problem gene from their father but she can not get the disease unless she also received the same problematic gene from her mother. It is possible that a person engaged with hunter syndrome whose family background is free from this type of disease.

What are Symptoms of Hunter Syndrome?

After birth, children do not show any type of related symptoms but when they reach the age of 2 and 4, they have enlarged lips, cheeks, nose, and tongue. Hoarse voice due to the enlargement of vocal cords. Respiratory infections due to narrowing of airways and during sleep breath pause are short. As this disease is increased, patients require medical treatment for the opening of their airways.

People with Hunter syndrome develop a large head, fluid is formed in brain cells, spleen, and liver increase in size, umbilical hernia, and inguinal hernia also form. They have thick skin that is stretched. Some people get patches of white skin which look like pebbles. Some infected persons have ear infections and loss of hearing occurs.

In the eyes of some individuals, problems occur in tissues of the eyes which play a role in light sensation which results in reduced vision. Hands and fingers are weak mostly in children. In the neck region, the spinal canal gets narrow and hurts the spinal cord. Many people are involved in heart problems, they have a large heart which leads to heart failure.

They develop short stature due to a slow growth rate. There is a formation of joint deformities in affected people and difficulties in movement. Affected individuals develop dysostosis multiplex. In the dysostosis multiplex, there are multiple abnormalities of the skeleton. It can be seen by x-rays. Especially the ribs bones get increased in size in case of dysostosis multiplex.

Types of mucopolysaccharidosis

One type is MPS II: include two types. It can be a severe type and another is a mild type. Severe and mild types cause various abnormalities in organs. MPS II people develop a loss of intellectuality. People who reach the age of 6 and 8, if they have severe type then there is a decline in numerous skills that perform specific functions.

other types of MPSs, are given below

MPS I: This is called Hurler syndrome.

MPS III: it is called Sanfilippo syndrome.

MPS IV: it is called Moquino syndrome.

Genetics of hunter syndrome

Individuals are nominated as hunter syndrome 1 in 162000 births. It is the x linked recessive trait. That particularly affects males. On the x chromosome, the IDS gene is present. Iduronate 2 sulfatase enzyme is encoded on that part of the gene such as the IDS gene. If there is the declination of the iduronate 2 sulfatase enzyme, then it propagates GAG (glycosaminoglycan) which leads to several permanent disorders.

As we know that 2 x chromosomes are present in females whereas one x chromosome is present in the case of a male. And also, one y chromosome.  Male carry x chromosomes from females and y chromosomes from the male.

In the case of a female, if she received one mutant IDS gene for hunter syndrome, that female also has a normal gene that is dominant over the mutant gene. And do not express the disease. In this case, she will behave like a carrier.

If she gets two mutant genes then there will be more chances for hunter syndrome. But in the case of a male, if he received a mutant gene during gamete formation, he will definitely show disorder because males have only one x chromosome. In this way, he will show x link recessive disorder.

In short, if the mother is a carrier, then she will pass the disease to 50% of their female and 50% of their male child. If the father has an infected gene, he will pass the disease to all his female children and none of their male children because the male child has only one x chromosome and that will be inherited from his mother.

What is diagnosis of Hunter Syndrome?

If a person represents any symptoms of hunter syndrome, then it will be more easily diagnosed by a doctor. And we called them a person with Hunter syndrome disorder. We can easily predict when several changes take place in an infected person’s face. These are abnormal facial changes. Normally it seems that changes take place between the age of 2 and 4, if we predict that then we go to the doctor for further tests for the confirmation of the disease.

For the confirmation of the disease main test which is done for it are given below ;

Blood test, urine test, and a sample of tissue tests.At the start, simple but important screening tests are done with urine samples. for the purpose of checking the accumulation of mucopolysaccharides MPS.

After this most of the people took blood samples to see the presence of iduronate 2- sulfatase enzymes. Also, the level of these enzymes is checked. We can also check the severity of the disease by iduronate 2 sulfatase by white blood cells and biopsy of the skin.

Sometimes there is a normal urine test even if the child has abnormal values of mucopolysaccharides. We can also diagnose hunter syndrome disease before the childbirth. This can be done by using parents.

From the mother, around the womb, fluid is present which we call the amniotic fluid. Amniocentesis is a process in which we use amniotic fluid for observing the amount of iduronate 2 sulfatase enzyme.

On the other hand, chorionic villus sampling in which we took the tissue sample of the maternal placenta and then we tested it.  In some time, hunter syndrome shows fewer symptoms because of the occurrence of other health problems. For example, a child is suffering from pneumonia and his ribs are shown by x rays of the chest which is resultant abnormal.

That is why, because of less propagation of the disease and quantity of signs shown by this disease, diagnosis is the time taken. If there is a carrier individual of hunter syndrome then we will easily predict the infected gene by DNA sequencing. And if there is a family disorder, genetically inherited then molecular genetic tests help us to diagnose the disease.

What is Treatment of Hunter Syndrome?

A fluid that is associated with developing a baby in the mother’s womb or takes the placenta tissue sample can identify the baby whether he or she carries the disease or not.

Dealing with respiratory complications

We can relieve the child from sleep apnea by removing the tonsils and adenoids which play a role in easily breathing during sleeping and open the respiratory tract. But this is not a permanent treatment, as the disease grows.

Today various breathing devices are introduced to open the airways such as continuous positive airways pressure CPAP or it is also known as bilevel positive airway pressure BiPAP. Through these devices, a child easily breathes during sleep apnea and also that infected child remains in an open environment so that there is no deficiency of oxygen.

Dealing with heart complications

An infected child is diagnosed, to see a heart problem. Doctors will examine the infected child’s heart and see the activity of heart valves, pumps, and blood pressure. If a doctor examines any problem in heart activity, then they decide to replace that heart with the normal functioning of the heart.

Dealing with skeleton and connective tissue abnormalities

Using inner hardware is the hardest work if we treat the bones which become totally weak. The main problem is that hunter syndrome people do not get well soon, they develop permanent disorders. If we try physical therapy on an infected child, there will be chances for them to perform function easily.

But this does not stop the pain and sudden stiffness in joints. If hernias are developed surgery may be beneficial to some extent but not considered as a cure. Because they have very weak connective tissues. One possibility is that we should use a framework of help instead of surgery.

Dealing with neurological complications

Infected children have excess brain fluid and also extra growth of tissues, doctors should have to expel all these fluids from the brain and also extra tissues. As this is very complicated work so they prefer case of seizures, anticonvulsants are given.

Dealing with behavioral abnormalities

Most of the time, a happy home environment helps a lot for an infected disease person. Because they feel safe at home and behave normally. This impact has more potential than by using medications because they cause side effects.

Dealing with sleep issues

Families should have to create a safe environment at home. They should have a regular schedule for sleeping. Because they suffer from serious sleeping problems. Sometimes doctors recommend sedatives but the home environment matters a lot.

Advanced treatment

In advanced treatment, physicians use various techniques to save an infected child or lessen the effects of the disease. These are given below

a)     Therapy of enzyme

In this treatment, genetically engineered people deal with replacing the missing or defective part of that functional gene with a normal one so that person does perform their function accurately. This type of treatment is done every week by a process called intravenous line.

By doing transplant enzyme therapy, we can stop the symptoms of hunter syndrome to some extent. Their expressions can be delayed. Its main advantage is that a defected person’s life can be significantly increased and live a better seems that a defected child does not express any improvement in his intellectual ability by this therapy.

Disadvantages of enzyme therapy are, it causes a severe type of allergic reaction, also causes fever headaches, but these all-side effects should be lower with the help of medication dose.

b)     Bone marrow transplant

To perform bone marrow therapy, it needs more research. But it’s assumed that the child develops loss and abnormal enzymes with the replacement of healthy stem cells into the child.

c)     Gene therapy

It also required great research to do gene therapy. It functionally has the potential to recover from hunter syndrome. In gene therapy, defected enzymes are present on chromosomes, and chromosomes should be removed with normal chromosomes. So that they function normally.


Numerous complications occur in the human body if hunter syndrome is shown in the body. It mainly depends upon which type of symptom is displayed and how severe it is. Complications of hunter syndrome have an effect on the heart, lungs, joints, connective tissue, brain, and nervous system of infected individuals.

  1.     Respiratory tract complication

In respiratory complications, individuals develop a large tongue, gum increases, passage of the nasal, and trachea are enlarged which makes breathing difficult. The ear gets chronic, sinus abnormalities, respiratory tract abnormalities, and sometimes causes pneumonia.

During sleep, difficulties in taking breaths appear. This disease is called sleep apnea. Sometimes disturbance is due to airway constriction.

  1.     Cardiac tissue complication

Heart valves get closed due to the enlargement of heart tissue. As a result, various body parts and organs do not get sufficient blood. As a result, the heart failure of individuals occurs. Size increases in tissue cause abnormalities in the aorta and various blood vessels. So that’s why there is an increase in blood pressure and arteries become narrow in lung tissue.

  1.     Skeletal and connective tissue

Most people suffer from problems in bones, joint tissues caused by accumulations of undigested complex macromolecules in bone cells. It seems that people feel difficulties in movement and feel pain all the time. They develop physically malfunctioning and also the growth of the child retards and gets slow.

  1.     Neurologic complication

A child with Hunter syndrome has numerous nervous disorders and brain complications.  It is thought that many nervous complications take place due to excess fluid present in the infected brain. When fluid is increased in the amount, they exert pressure on the brain and cause other sensations like severe headaches and they also face problems with vision and they also face abnormal mental health.

Risk factor

Hunter syndrome develop two major risk factors

  • Family history
  • Sex

Family history

Hunter syndrome is due to abnormal chromosomes, and a person transfers a disease to their progeny (inherited disease). We know that hunter syndrome is the disease that we normally call x linked recessive. Which is definitely transfer from mother because x chromosome in male transfer from mother and cause disease in male.

On the other hand, the mother is phenotypically normal because another x chromosome is normal in the mother which does not show the trait of defective disease. We know the mother as a carrier of a disease.


As we discussed earlier, hunter syndrome is at high risk to develop in males this is just because of only one x chromosomes they carry that’s why they show his phenotype as a disease. But in the case of females, they do not show the disease just because of two x chromosomes if one is a defective gene then another normal gene dominant over the defective gene. And suppressed his phenotype.

Expectancy life of hunter syndrome

Hunter syndrome reduces the life of a person. It should be approximately 10 to 20 years approximately.


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