Mucopolysaccharidosis type I (Hurler, Hurler-Scheie and Scheie syndromes)

Mucopolysaccharides are long chains of sugar molecules used to build bones, cartilage, skin, tendons and other tissues. The body constantly builds new ones and recycles old ones, and recycling needs a series of enzymes. In MPS I the enzyme alpha-L-iduronidase is missing or low, so two of these sugars, dermatan sulphate and heparan sulphate, stay in the cells.

A baby may look well at first. Symptoms emerge as more and more cells fill with partly broken-down material, which is why a diagnosis can come some time after the first symptoms. Medical references now sometimes describe MPS I as severe and attenuated types rather than three separate syndromes, because the features overlap so much.

Children with classic Hurler disease usually have developmental delay that progresses, with severe physical problems and early advancement of the disease. Babies are often larger than average and grow quickly until about their first birthday, after which growth slows markedly and then stops at around the age of 3 years.

People with Scheie disease do not have progressive developmental delay and their physical problems advance more slowly. Some look much like other people except for a short, stiff neck, thickened lips and a square jaw. Hurler-Scheie falls between the two ends. It is common for the label to be refined over time as a person develops.

• Hurler: facial features described as coarse, prominent abdomen, a hump in the upper spine, short stature, and a characteristic way of walking and holding the arms.

• Hurler-Scheie: variable height, sometimes a short trunk compared with the legs, with a gradually developing walking pattern.

• Scheie: near-normal height and lifespan are possible, with joint stiffness, corneal clouding and heart valve disease more prominent.

Joint stiffness occurs in every form. Shoulders, arms, hips and knees lose movement, which makes dressing and everyday tasks harder, and warmth and painkillers are used for discomfort. Nearly all children with Hurler disease need spinal surgery or a spinal support at some point, because poorly shaped vertebrae produce a hump in the upper back.

Hands become short and broad with fingers that curve over. Thickened ligaments can press on nerves and cause carpal tunnel syndrome, which a nerve conduction study can confirm and an operation can relieve. Hurler-Scheie and Scheie disease can bring lower back pain from slipped vertebrae.

Medical genetics summaries also list heart valve disease, an enlarged liver and spleen, hernias, clouding of the cornea, hearing loss with recurrent ear infections, a narrowed airway with sleep apnoea, and compression of the spinal cord in the neck. Heart disease and airway obstruction are recognised major causes of death in both types.

The first clues are usually a cluster of features: hernias, a large head, stiff joints, recurrent ear and chest infections and a change in facial appearance. A paediatrician or GP who suspects an MPS condition refers on to a specialist metabolic or lysosomal service, where urine and blood tests look for the stored sugars and measure enzyme activity. Genetic testing then confirms the variants involved.

Because the same gene change can behave differently between families, the specialist team assesses the whole picture: development, airway, heart, eyes, hearing, spine and hands. That assessment decides whether a child is offered transplant or enzyme replacement.

For Hurler disease, haematopoietic stem cell transplantation is the treatment of choice for children up to 2 years old. The immediate benefit is correction of the missing enzyme, and the long-term benefit is a longer life through protection of heart, lungs and brain from progression. Eyes, ears, liver, spleen, joints and airways can also benefit. Many people still need orthopaedic surgery afterwards. Enzyme replacement is given for a short time before and after the transplant.

For Hurler-Scheie and Scheie disease, enzyme replacement with laronidase is a long-term treatment given by infusion. It was licensed in 2003 and has been shown to improve respiratory function and mobility and reduce joint stiffness. It does not treat brain-related symptoms. The infusion is weekly, lasts 3 to 4 hours and is usually given at home once the family is trained.

Alongside these, care is multidisciplinary: orthopaedics, cardiology, anaesthetists who understand the difficult airway, audiology, ophthalmology, physiotherapy and educational support. Anaesthesia in particular needs planning in a centre that knows the condition.

MPS I is autosomal recessive, so each pregnancy for two carrier parents carries a 1 in 4 chance of an affected baby, independent of earlier children. Genetic counselling is offered through the specialist centre or GP, with referral to a regional genetics service. Options described by the MPS Society include early testing in pregnancy by amniocentesis or chorionic villus sampling, and pre-implantation genetic testing with IVF. Carrier screening has limits and is not possible in every case.

During a 10-year period (1989 to 1999) the MPS Society reports that 88 babies were born with MPS I in the UK, which gives a sense of how few families are affected. Support, home visits and signposting to social care, adaptations and education are provided by the charity.

Seek urgent medical care for new weakness, numbness or difficulty walking, which can signal spinal cord compression, and for noisy or laboured breathing, long pauses in breathing during sleep, or choking. Contact the specialist team promptly for any planned surgery or sedation so the anaesthetic risks are known. In an emergency call 999.