Clinical Presentation

This information sheet addresses a wide range of possible symptoms and presentations of MPS VI. However, an affected person may not experience them all or to the degree described here. Treatment may improve some of these features (see Treatment, below).

 

Growth

Growth is usually restricted, but final height may range from about three-feet (95 cm) to six-feet (180 cm). In general, the short stature is not in proportion and the trunk is usually shorter than the legs.

 

Facial Appearance

Those with more severe disease tend to bear a close resemblance to each other. Their faces are often chubby; their neck is often short and the nose broad with a flattened bridge; their lips are often thickened and the tongue may become enlarged.

 

The appearance of those with less severe disease is variable and some may only experience a mild change in their facial appearance.

 

Intellectual Ability

Mucopolysaccharide storage does not occur in the brain and intelligence is usually not affected.

 

However, in all individuals with MPS VI the ability to learn may be affected by other complications of the disorder that are not directly related to the brain. For example, deafness may make it more difficult to learn spoken language; limitations of hand movements may slow the development of fine motor skills such as writing. This emphasises the importance of being aware of the various problems associated with the disorder to maximise quality of life.

 

Eyes

The outer layer at the front of the eye (the cornea) may become cloudy due to mucopolysaccharide storage and affect vision, especially in dim light. Bright light may be a problem for some people: wearing caps with broad visors and sunglasses may help. If clouding becomes so marked that vision is severely restricted, a corneal graft may be possible.

 

Occasionally, vision may be affected by changes to the retina, or glaucoma (increased fluid pressure inside the eye). Mucopolysaccharide storage in the retina can result in loss of peripheral vision and night blindness. Night blindness may make a person not want to walk in a dark area, or wake up at night and be afraid; the use of a night light or lamp may help. If vision is a concern, examination by an eye doctor (ophthalmologist) is recommended.

 

Head

The head may be large with a prominent forehead but this does not usually cause any problems.

 

A condition known as hydrocephalus may develop. This is caused by a build-up of the fluid that surrounds the brain (the cerebrospinal fluid, or CSF). Thickening of tissues around the brain may obstruct the circulation and absorption of this fluid and cause pressure on the brain. This may lead to symptoms such as headache, vomiting or drowsiness; the head may also increase in size. Hydrocephalus needs to be monitored closely and can be treated surgically, if necessary, usually by the insertion of a shunt (a tube placed inside the skull to help drain the excess fluid, usually into the abdomen).

 

Nose

The bridge of the nose may be flattened, and the passage behind the nose may be smaller than usual due to poor growth of the bones in the mid-face and thickened soft tissue in the nose and throat, and lead to narrowing of the airway. Chronic drainage of clear mucus from the nose (rhinorrhea) may occur, which is due to the abnormal drainage of normal secretions, and chronic ear and sinus infections.

 

Throat

The tonsils and adenoids often become enlarged and may narrow the airway. This, combined with a short neck, contributes to breathing problems. The windpipe (trachea) can become narrowed by thickened tissue and may be floppy or softer than usual due to abnormal cartilage rings in the trachea.

 

Chest

The shape of the chest is usually abnormal and the junction between the ribs and the breastbone (sternum) may not be very flexible. The chest can therefore become rigid and unable to move freely to allow the lungs to take in a large volume of air. The muscle at the base of the chest (diaphragm) may also be pushed upward by the enlarged liver and spleen, further reducing the space for the lungs. When the lungs are not fully cleared, there is an increased risk of infection (pneumonia). These changes also affect breathing, and can cause breathlessness and reduced endurance. Lung function and walk tests can help monitor these problems and assist with management.

 

Breathing Problems

Noisy breathing is common even when there is no infection, and restlessness and snoring may be a problem at night. If there is narrowing of the large airways and increased secretions there is increased risk for asthma-like episodes: treatment with asthma medication during chesty illnesses may help decrease cough and ease breathing. A lung specialist can help determine if asthma-like episodes are occurring.

 

Sleep apnoea (not breathing for short periods whilst asleep) is common and may be a sign that the oxygen level is low during sleep, which can damage the heart over time. (Note: pauses of up to 10-15 seconds may be normal.) The noisy breathing, which may stop and start, can be very frightening for parents. If significant choking or episodes of interrupted breathing whilst sleeping are being experienced, evaluation by a sleep specialist is recommended. It is important to know that many individuals may breathe like this for years.

 

Management of airways and breathing problems

Sleep studies measure the blood oxygen level, breathing effort, brain waves during sleep and other monitors of the body’s function.  A sleep study is likely to require an overnight stay in hospital.

 

If sleep apnoea is a problem, treatment with continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) may be needed during sleep. This involves placing a mask on the face each night and having air pumped into the airway to keep it open. This may seem extreme but is usually well tolerated because it can improve sleep quality as well as help prevent or reduce the risk of heart failure caused by low oxygen.

 

In severe cases of sleep apnoea or breathing difficulties, a hole may need to be opened in the airway at the front of the neck and a breathing tube inserted (this is known as a tracheotomy). This is a significant and invasive procedure that needs to be discussed with your doctor.

 

Chest postural drainage can be helpful in clearing secretions from the lungs to improve breathing. A physiotherapist will be able to teach parents, teachers and caregivers how to do this.

 

Respiratory Infections

Frequent coughs and colds are common.

 

Medication can affect individuals differently, so it is advisable to consult your doctor before using over-the-counter medicines. Drugs to control mucus production may not help: antihistamines, for example, may dry out the mucus, making it thicker and harder to dislodge. Decongestants usually contain stimulants that can raise blood pressure and narrow blood vessels, both undesirable in MPS VI. Cough suppressants or drugs that are too sedating may cause problems with sleep apnoea by depressing muscle tone and respiration.

 

Secondary bacterial infections of the sinuses or middle ear may occur and require treatment, usually with antibiotics. Poor drainage of the sinuses and middle ear can make overcoming infections difficult: infections may improve whilst taking medication but promptly recur after it is stopped. Chronic antibiotic therapy may help with recurrent ear infections. Ventilation tubes can be used to improve drainage from the ear and help resolve infections: an ear, nose and throat (ENT) specialist will advise on which tube is best.

 

Infections that do not respond to antibiotic treatment may develop. Other medications can be prescribed to help manage this problem if it occurs. While over-using antibiotics is not advised, most individuals will require some type of treatment for most infections.

 

Ears

Some degree of deafness may occur. It may be conductive or nerve deafness or both (mixed deafness) and may be made worse by frequent ear infections. It is important that hearing is monitored regularly so problems can be treated early to maximise the ability to learn and communicate.

 

Conductive Deafness is due to impaired transmission of sound waves through the ear canal, the ear drum and the middle ear. Correct functioning of the middle ear depends on the pressure behind the ear drum being the same as that in the outer ear canal and the atmosphere. This pressure is equalised by a tube in the ear called the Eustachian tube, which runs from the middle ear to the back of the nose. If the tube is blocked, the pressure behind the ear drum will drop and the drum will be drawn in. The transmission of sound waves will then be impaired. If this negative pressure persists, fluid from the lining of the middle ear will build up and in time become thick, like glue, hence the condition being known as ‘glue ear’.

 

Under general anaesthetic a small incision can be made in the ear drum (myringotomy) and the fluid sucked out. A small ventilation tube called a ‘grommet’ may then be inserted to keep the hole open and allow air to enter from the outer ear canal until the Eustachian tube starts to work properly again. Grommets will eventually fall out. If the conductive deafness recurs, T-tubes (a type of grommet which stays in place longer) may be used. Due to the anaesthetic risks in MPS VI (see Anaesthetic, below), the surgeon may decide to use T-tubes on the first occasion.

 

Sensorineural (nerve) deafness: in most cases nerve deafness is caused by damage to the tiny hair cells in the inner ear. It may accompany conductive deafness in which case it is referred to as ‘mixed deafness’. Nerve deafness is managed by the fitting of hearing aids. Some individuals may keep pulling out their hearing aids at first but it is important to persevere at wearing them to maintain communication.

 

Mouth and Teeth

The tongue may become enlarged; gum ridges can be broad, and the teeth widely spaced and poorly formed with fragile enamel. It is important to look after the teeth as tooth decay can be a cause of pain. Teeth should be cleaned regularly, and if the water in your area is not treated with fluoride it is advisable to give tablets or drops daily. Cleaning inside the mouth with a small sponge on a stick soaked in mouthwash will help keep the mouth fresh. Even with the best dental care, an abscess around a tooth can develop due to abnormal formation of the tooth.  Irritability, crying and restlessness can sometimes be the only sign of an infected tooth.

 

If an individual has a heart problem, it may be advisable to give antibiotics before and after any dental treatment. This is because certain bacteria in the mouth may get into the bloodstream and cause an infection in an abnormal heart valve, potentially damaging it further.

 

If teeth need to be removed while under an anaesthetic, it should be done in the hospital under the care of both an experienced anaesthetist and a dentist – never in the dentist’s office.

 

Heart

Heart disease is common. High blood pressure may occasionally be a problem.

 

Heart murmurs (sounds caused by turbulence in blood flow in the heart) may develop if the valves become damaged as the disorder progresses. Heart valves close tightly as blood passes from one chamber of the heart to another to stop blood flowing back in the wrong direction. If a valve is weakened, it may not shut firmly enough and a small amount of blood may shoot backward, leading to turbulence and a murmur. The opening of the valves may also become narrowed and make it more difficult for the heart to pump the blood properly.

 

Slowly progressive valvular heart disease may be present for years without any apparent clinical effects. If the condition worsens, however, medications can be used to lessen the effect on the heart. Sometimes, an operation may be required to replace the damaged valves.

 

The more serious, life-threatening problem of thickening and weakening of the heart muscles can be present at birth.

 

Occasionally, the coronary arteries may become narrowed and cause episodes of chest pain (angina). If the person is distressed and is also pale and sweating while keeping still, medical advice should be sought.

 

Your doctor may recommend a test known as an echocardiogram as often as necessary to monitor the heart. The test is painless and similar to ultrasound screening of babies in the womb.

 

Skin

The skin may become thickened and lack elasticity, which can cause irritation and soreness, particularly in areas where the skin folds, e.g. at the back of the neck. The skin may also develop a characteristic pebble-like texture. Occasionally, there may be more body hair than normal: this is called hirsuitism.

 

Liver and spleen

The liver and spleen may become enlarged (hepatosplenomegaly). This does not usually lead to liver failure but it may interfere with eating and breathing and the proper fitting of clothes.

 

Abdomen and hernias

The abdomen may bulge out due to posture and weakness of the muscles, as well as the enlarged liver and spleen. Part of the abdominal contents may push out from behind a weak spot in the wall of the abdomen: this is called a hernia. Hernias can come from behind the navel (umbilical hernia) or in the groin (inguinal hernia). Inguinal hernias can be surgically repaired but will sometimes recur. Umbilical hernias are not usually treated unless they are causing problems: it is common for an umbilical hernia to recur after a repair has been made.

 

Bowel problems

Loose stools and diarrhoea are common. The cause of this is not fully understood. Occasionally, it results from severe constipation and leakage of loose stools from behind the solid mass of faeces. More often, however, parents describe it as “coming straight through”. A medical examination may establish the cause. It may disappear with time but it can be made worse by antibiotics prescribed for other problems.

 

The episodic diarrhoea may be affected by diet; elimination of some foods may help. If antibiotics are the cause, eating plain live-culture yoghurt can provide a source of ‘good bacteria’ to help prevent the growth of harmful bacteria within the bowel: a diet low in roughage may also help.

 

If constipation is a problem, an increase in roughage in the diet may assist. If this does not help or is not possible, laxatives or a disposable enema may be needed.

 

Bones and Joints

The formation and growth of bones and joints is impaired in MPS VI. Some people may develop stiff hips because the supporting socket is not formed properly. Joint pain may develop. Pain may be relieved by warmth and the prescribing of analgesics (pain relievers). Surgery on the hips may be possible if pain becomes a real problem. Limited movement in the shoulders and arms may make dressing, toileting and self-care (e.g. brushing hair) difficult. Anti-inflammatory drugs, such as ibuprofen, can help with joint pain but they should be taken with or after food and monitored closely to prevent stomach irritation and ulcers.

 

Recent research has shown that high-dose vitamin D therapy can improve mineral bone density. Sensible exposure to sunlight will help maintain vitamin D levels.

 

Spine and Cervical Spine

The bones that support and surround the spinal cord down the back are known as vertebrae. The cervical spine refers to the bones that support the neck. The spinal column is the ’backbone’, which is made up of the individual vertebrae that sit on top of each other from the base of the spine (the coccyx) to the base of the skull.

 

In MPS VI, the vertebrae in the middle of the back are sometimes small and mis-shaped, and one or two may be set back in line. This can produce a kink (known as gibbus). This is unlikely to need treatment but if it is causing problems surgery may be needed to straighten the spine.

 

The spinal cord passes down the spinal column through a passage known as the spinal canal. The space in this canal may be gradually reduced by thickening of the tissues in and around it, and lead to compression of the spinal cord, weakness in the limbs or even paralysis. This is particularly a problem in the neck (cervical spine) where the spinal cord comes out through the space in the base of the skull bone. More rarely, compression may result from structural defects in the upper vertebrae leading to instability. Both problems can be treated surgically if necessary.

 

Your doctor may recommend regular imaging scans of the cervical and lower spine using magnetic resonance imaging (MRI) and plain X-rays as needed.

 

In general, care should be taken with the spine. It is recommended that high risk activities such as contact sports and gymnastics, including trampolines, are avoided.

 


Legs and feet

Many individuals with MPS VI stand and walk with their knees and hips flexed. This, combined with a tight Achilles tendon, may cause them to walk on their toes. Knock-knees can sometimes be a problem; this is unlikely to need treatment but surgery may be required if severe. The feet are often broad and may be stiff with the toes curled under, rather like the hands.

 

Hands

The hands are usually short and broad with stubby fingers that gradually become curved over or ‘clawed’ as the disorder progresses.

 

Carpal Tunnel Syndrome

Carpal tunnel syndrome is common. One of the (two) nerves to each hand pass through a narrow space in the wrist known as the carpal tunnel. This space may become narrowed due to thickening of tissues and result in compression of this nerve. Although pain in the hands may not be a problem, carpal tunnel syndrome may already be present. This can be tested by a nerve conduction study. This test would also be done if there is weakness or numbness in the hand or decreased muscle mass at the base of the thumb. This problem may be treated by surgery on the wrist, where the nerve may be compressed. A similar problem can affect the feet, in which case it is known as tarsal tunnel syndrome.

.