Clinical Presentation

This information sheet addresses a wide range of possible symptoms and presentations of MPS III. However, an affected person may not experience them all or to the degree described here.

 Physical and mental development may be normal at first. The rate at which mental decline will occur may be difficult to predict early on. Declining brain function and associated problems with behaviour and communication may make medical examinations difficult. It is important that simple and treatable problems such as ear infections and toothaches are not overlooked as a cause of pain or distress. These children may have an increased tolerance of pain or may find it difficult to communicate that they are in pain. Do not hesitate to consult a doctor if you think your child might be in pain.

 Growth

People with MPS III grow to a fairly normal height.

Facial Appearance

Changes in appearance may gradually develop with time. The eyebrows may be dark and bushy and meet in the middle; the hair tends to be thick.

 Intellectual Ability

Generally, intellectual development slows down by about 2 to 4 years of age, followed by a gradual loss of skills. However, the pattern is varied: some will only learn to say a few words while others may learn to talk and read a little. Emphasis should be on helping infants and children learn as much as they can before the disorder progresses.

 Milder learning difficulties may be experienced by those whose disorder is less severe or later-onset. However, as brain function declines intellectual ability is likely to worsen.

However, in all individuals with MPS III 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. This emphasises the importance of being aware of the various problems associated with the disorder to maximise quality of life.

Eyes

Clouding of the cornea (the outer clear layer of the eye) does not usually develop.

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

Although not common, 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. Symptoms may include an increase in the size of the head, vomiting or drowsiness. 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 that helps 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 may become enlarged and may narrow the airway. If required, the adenoids can be surgically removed.

Breathing Problems

Sleep apnoea (not breathing for short periods whilst asleep) is not common but a person may sometimes stop breathing for short periods. It 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 stop-start breathing can be very frightening for parents. If significant choking or episodes of interrupted breathing whilst asleep 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.

Chest postural drainage can also be helpful in clearing secretions from the lungs to improve breathing. A physiotherapist will be able to teach parents 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 III. 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 speed resolution of 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

Deafness is common: 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 III (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 fluoride 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 dentist – never in the dentist’s office.

Heart

Serious heart problems rarely occur in MPS III. If heart problems do develop, however, they may not cause any real problems until later in life.

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. Some degree of heart valve leakage or blockage is common, but it is usually mild and surgery is rarely needed.

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.

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.

Liver and spleen

The liver and spleen may become enlarged (hepatosplenomegaly). This does not usually lead to live 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 or weakness of the muscles. 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 be helpful.

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.

Skin

The skin is generally soft and has greater elasticity than in the other MPS disorders. However, thickening of the skin can occur as the disorder progresses. Excess hair on the face and back may also occur: this is called hirsuitism.

Bones and Joints

Problems with bone formation and growth are usually minimal. Features of osteoporosis can, however, develop as early as the teen years. As the bones become fragile and brittle there is an increased risk of fractures, and the decrease in overall stability increases the risk of falling. Prolonged use of anti-seizure drugs combined with decreased mobility can lead to brittle bones. Recent research has shown that high-dose vitamin D therapy can improve bone mineral density. Sensible exposure to sunlight will help maintain vitamin D levels.

Joint problems are also minimal but later in life joint stiffness may cause pain, which can be relieved by warmth and the prescribing of analgesics (pain relievers). 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.

Hips

The hips may become dislocated, usually due to muscle spasms and after the ability to walk is lost. Often, this does not cause problems and treatment may be unnecessary unless it is causing pain or other disability.

Cervical Spine

The cervical spine refers to the bones that support the neck. Whilst bone problems are not common in MPS III, the spinal cord may be gradually compressed by surrounding tissues, which are thickened, partly as a result of mucopolysaccharide storage or, more rarely, by structural defects in the upper vertebrae (bones) of the spine that results in instability. This can lead to weakness in the limbs and even paralysis. Both problems can be treated surgically if necessary.

Legs and feet

Over time, a tendency to stand and walk with the knees and hips flexed may develop. This, combined with a tight Achilles tendon, may cause a person to walk on their toes. Knock-knees can sometimes be a problem; this is unlikely to need treatment but, if severe, surgery may be required.

Hands

The fingers may contract and bend at the joints, and fully extending the arms may become difficult as the disorder progresses.

Cold hands and feet

As the disorder progresses, the part of the brain that regulates temperature may become damaged and result in cold hands and feet. It may not cause discomfort, but if it does the obvious remedies of heavy socks and warm gloves may be useful. In the later stages, sweating may become a problem at night, as well as cold hands and feet by day. Body temperature may sometimes drop (hypothermia): if this happens, they should be kept warm and medical advice sought on the best ways of managing the problem.

Movement disorders

A variety of movement problems have been reported in teenagers, beginning with eye fluttering, fast breathing and extreme restlessness. This can lead to sweating, arm and leg jerking and kicking and, in some cases, spasms with rigid arms and legs. These may or may not be linked to seizures and can be difficult to treat. Some individuals may appear to be in pain, while others may not. Therapies such as physical therapy, massage and water therapy have been tried, with varied success. Medical advice should be sought on the best ways of managing the problems.

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