This page gives an organ by organ overview for families and healthcare professionals, showing how the same underlying problem in lysosomes leads to different symptoms in different parts of the body.
Key body systems affected in Hurler syndrome
Select a system to learn more about how Hurler syndrome affects that part of the body
Teeth and mouth
- Brain and nervous system
Brain and nervous system
In severe MPS I, GAG storage occurs in neurons, glial cells, meninges and blood vessels in the brain and spinal cord. This can lead to progressive developmental delay, loss of skills, behavioural changes and problems with walking or balance. Many children also develop hydrocephalus and spinal cord compression at the neck.
Typical features:
- Developmental delay in the first years of life
- Slowing then loss of previously learned skills in untreated children
- Behavioural difficulties, anxiety or sleep problems
- Hydrocephalus (fluid build up around the brain)
- Cervical spinal cord compression causing weakness, pain or instability
- Bones and joints
Bones, joints and skeletal system
GAG storage in growth plates, cartilage and bone leads to a pattern called dysostosis multiplex. This affects almost every bone. Children may have a short trunk, curved spine, abnormal hips, knock knees, joint stiffness and reduced height. Skeletal problems often progress even after HSCT or ERT and are a major cause of pain and disability in older children and adults.
- Short stature and disproportionate growth
- Characteristic skull, spine, rib and pelvis changes on x ray
- Hip dysplasia and risk of early hip dislocation
- Genu valgum (knock knees) and other limb deformities
- Joint stiffness, contractures and reduced range of movement
- Carpal tunnel syndrome and other nerve entrapments
- Heart and circulation
Heart and circulation
GAGs accumulate in heart valves, myocardium and blood vessel walls. Most children with Hurler syndrome develop valve thickening, usually affecting the mitral and aortic valves. This can lead to valve leakage, heart enlargement and eventual heart failure. Some patients also have involvement of the coronary arteries and aortic root.
- Thickened heart valves with regurgitation (leakage)
- Thickened heart muscle and cardiomyopathy in some patients
- Enlargement of the heart and reduced pumping function over time
- Increased risk during anaesthesia and surgery
- Lungs and airways
Lungs, airways and breathing
GAG deposition in the nose, tongue, tonsils, adenoids, larynx and trachea leads to airway narrowing. Combined with chest wall deformity and weak respiratory muscles, this causes noisy breathing, obstructive sleep apnoea and recurrent chest infections. Airway problems are a key risk around anaesthesia.
- Noisy breathing and snoring, especially at night
- Obstructive sleep apnoea with frequent awakenings or daytime sleepiness
- Frequent chest infections and chronic cough
- Reduced exercise tolerance and breathlessness
- Difficult airway for anaesthetists during operations
- Liver and abdomen
Liver, spleen and abdominal organs
GAG storage in the liver and spleen causes hepatosplenomegaly. Many babies and toddlers with Hurler syndrome also have umbilical or inguinal hernias. Although liver and spleen enlargement rarely cause early organ failure, they reflect the degree of systemic storage and can contribute to abdominal discomfort.
- Enlarged liver and spleen on examination or ultrasound
- Umbilical and inguinal hernias, often appearing in infancy
- Protruding abdomen
- Occasional problems with appetite or constipation
- Eyes and vision
Eyes and vision
In Hurler syndrome, GAGs accumulate in the cornea, retina and other ocular tissues. Corneal clouding is common and can progress, reducing clarity of vision. Some patients develop retinal degeneration, raised eye pressure or optic nerve problems.
- Corneal clouding, which may be visible as a hazy or bluish cornea
- Reduced visual acuity and sensitivity to light
- Retinal changes that can affect night or peripheral vision
- Risk of optic nerve involvement and visual field loss
- Ears and hearing
Ears, hearing and speech
Ear and hearing problems are very common in Hurler syndrome. Thickened tissues and Eustachian tube dysfunction lead to recurrent middle ear infections and glue ear. Over time, both conductive and sensorineural hearing loss can develop. Hearing difficulties combine with developmental delay and enlarged tongue to affect speech.
- Frequent ear infections in infancy and childhood
- Glue ear with fluid behind the eardrum
- Conductive hearing loss, later often mixed or sensorineural
- Delayed or unclear speech and language
- Teeth and mouth
Teeth, mouth and airway space
GAG storage in gums, tongue and jaw bones causes thickened gums, enlarged tongue and crowded teeth. Combined with midface underdevelopment, this reduces space in the mouth and upper airway and contributes to snoring and obstructive sleep apnoea.
- Macroglossia (large tongue) and thickened gums
- Crowded or widely spaced teeth and delayed eruption
- Higher risk of dental decay and infection
- Contribution to speech difficulties and airway obstruction
A whole body condition that needs whole team care
The same biochemical problem in Hurler syndrome causes different problems in different organs. Some, such as liver enlargement, may improve significantly with treatment. Others, particularly bones, joints, heart valves and airways, can remain challenging even when enzyme levels are corrected.
This is why care for MPS I-H is centred in specialist metabolic and transplant hubs, with coordinated input from cardiology, respiratory medicine, neurology, neurosurgery, orthopaedics, ENT, ophthalmology, dentistry, physiotherapy, occupational therapy and psychology.
Key message for families:
You do not have to manage all of these problems alone. A multidisciplinary team can help plan investigations, treatment and follow up for each affected system over time.
What is Hurler syndrome?
Overview of the condition and how it is classified
Pathophysiology
How GAG storage and lysosomal dysfunction cause organ damage
Symptoms and diagnosis
Early signs, red flags and diagnostic tests
Treatments and care
HSCT, ERT and supportive management for each system