Mucopolysaccharidosis type IV (Morquio syndrome)

MPS IV was first identified by Dr Morquio in 1929. Two types exist. In MPS IVA the enzyme N-acetylgalactosamine 6-sulfatase is missing or low, and keratan sulphate and chondroitin sulphate accumulate. In MPS IVB beta-galactosidase is missing or low and keratan sulphate accumulates. Clinical features are similar, but are usually milder in type B.

Babies grow normally at first, then growth slows markedly at around 18 months. Severely affected children usually stop growing around 8 years of age and may reach a final height of between 90 and 120 cm, while others keep growing into their teens and may reach about 150 cm. The short stature is out of proportion, with a trunk that is relatively short compared with the legs.

Facial features include a wide mouth, an enlarged tongue, a prominent chin or square jaw and a flattened nose bridge, and widely spaced teeth with fragile enamel. Unlike other MPS conditions the hair texture is not affected. Joint contractures at shoulders, elbows, hips, knees and ankles give a characteristic way of walking and holding the arms, and a prominent abdomen is common.

The ankles can be weak and turn inwards, and flat feet are common because ligaments and tendons are weakened. Wrists may be enlarged and become loose and floppy as the small carpal bones fail to develop properly, which can cause considerable loss of hand power. Dental, cardiac, hearing, vision and breathing problems are also recognised.

In MPS IV the odontoid process, a peg of bone that normally supports the top of the spine between the first and second vertebrae, may fail to develop. The spinal cord is then insufficiently protected. Vertebrae can slip backwards and narrow the spinal canal, and the spine can curve sideways, forwards or both.

Squeezing of the spinal cord is a serious complication that needs careful clinical management. Chronic damage leads to a gradual loss of power in arms and legs. For this reason every person with MPS IV should be referred to an orthopaedic surgeon and the spine kept under regular review. If cervical instability is found, a cervical fusion may be recommended to prevent cord damage. After the operation it is essential to keep the neck in the correct position for three to four months.

• Report new numbness, tingling, clumsiness, change in walking, bladder or bowel change or neck pain promptly to the specialist team.

• Tell anaesthetists, dentists and paramedics about neck instability before any procedure, because positioning the neck can cause harm.

For MPS IVA, elosulfase alfa replaces the missing enzyme. It was licensed in the EU in 2014 and approved for use in MPS IVA in the UK in 2015. It is a weekly infusion lasting 4 to 5 hours that is usually administered at home. The MPS Society describes it as leading to less physical deterioration and reduced disability, with some people having more energy, but it is unlikely to reduce certain complications such as spinal cord damage.

NICE first dealt with elosulfase alfa through a managed access agreement, and its later highly specialised technologies guidance, published on 20 April 2022, recommends it as an option for treating MPS 4A in people of all ages, provided the company supplies it under the commercial arrangement. There is no equivalent enzyme for MPS IVB.

Surgery, physiotherapy, pain management, breathing assessments and hearing and eye checks make up the rest of the care plan.

Since intelligence is usually normal, most people with MPS IV follow a mainstream education, although fatigue, mobility, pain and frequent medical appointments need planning. The MPS Society lists a research poster on the educational and employment history of adults with MPS IVA and personal accounts from people who work, study or travel. A wheelchair or powered mobility is common as people get older, and housing and workplace adaptations can be arranged through occupational therapy and local authorities.

MPS IV is autosomal recessive, with a 1 in 4 chance in each pregnancy for two carrier parents. The MPS Society reports 26 babies born with MPS IV in the UK in a 10-year period from 1989 to 1999, which shows how rare it is. Genetic counselling covers testing for relatives, early testing in pregnancy and pre-implantation genetic testing options.

Call 999 for sudden weakness in the arms or legs, loss of bladder or bowel control, severe neck pain after a fall or accident, or severe breathing difficulty. Do not move the neck if a neck injury is suspected, and tell responders that the person has MPS IV.