Mucopolysaccharidosis type II (Hunter syndrome)

Hunter syndrome was first described in 1917 and is one of the mucopolysaccharide storage diseases. The missing enzyme, iduronate 2-sulphatase, is needed to break down dermatan sulphate and heparan sulphate. When these are not fully recycled they stay in cells, and the build-up produces the symptoms.

Babies may show little sign of the disease and the first features, such as frequent infections, stiff joints or a gradual change in facial appearance, are easily put down to common problems. That is why the diagnosis commonly arrives after a toddler has had several unrelated referrals.

The gene for the enzyme sits on the X chromosome. A boy has one X, so a single faulty copy causes the condition. A girl has two, so a working copy usually protects her and she is a carrier. The MPS Society notes that only in very rare cases are females affected.

For a female carrier, there is a 50% chance that any son will have MPS II and a 50% chance that any daughter will be a carrier, and these odds are independent of what happened in earlier pregnancies. Sisters and maternal aunts of an affected boy may be carriers too, so family testing and genetic counselling are routine parts of care.

Older descriptions split MPS II into mild and severe forms. Current understanding treats it as a continuum. Some boys have progressive developmental delay as well as severe physical problems. Others keep normal intelligence and have progressive physical disease of varying degrees. Effects can differ between siblings and across generations in a family.

Growth is often faster than usual during the first two years, then slows. Average adult height is reported as lower in more severely affected people than in those with the attenuated form. Skin can be thickened and may show small pebble-like bumps over the shoulder blades, upper arms and thighs. Temperature control can be poor because the brain centre that regulates it may be affected.

• Appearance: broad nose with a flattened bridge, thick lips, enlarged tongue, widely spaced teeth with fragile enamel, bushy eyebrows and extra body hair in some.

• Bones and joints: stiff joints, short broad hands, carpal tunnel syndrome, a mild upper-back hump and, occasionally in older children and adults, compression of the spinal cord in the neck.

• Other systems: heart, lungs, liver and spleen, eyes, hearing and teeth can all be involved.

Suspicion usually follows a pattern of features rather than one test. Referral is to a specialist metabolic or lysosomal centre, where urine tests for stored sugars and a blood test for enzyme activity are done, followed by genetic testing of the iduronate 2-sulphatase gene. A genetic result is important for the whole family because it tells female relatives whether they are carriers.

Idursulfase (Elaprase) replaces the missing enzyme by intravenous infusion each week. It was licensed in 2007 and has been shown to reduce many non-brain symptoms, including improving breathing function and mobility and reducing joint stiffness. The infusion lasts between 1 and 3 hours and can be given at home. People who receive it have reported softening of hair and facial features, taller height and a smaller abdomen as the enlarged organs reduce.

The standard enzyme does not cross into the brain effectively, so it does not treat learning difficulties. The MPS Society has also reported on regulatory developments for newer approaches aimed at the neurological side of MPS II, which families can discuss with their specialist team; these are not routine NHS treatment and eligibility depends on the product and the clinical situation.

Supportive care is important at every stage: physiotherapy, occupational therapy, ENT care for ears and airway, sleep studies, heart checks, dental care and educational planning.

Because cognitive ability varies so much, an education, health and care plan based on the individual, not on the diagnosis, is the usual route to the right school support. The MPS Society has research posters on diagnosis and treatment in the UK and on education in MPS II, and offers home visits, an active listening service and signposting to social care and benefits.

Call 999 for severe breathing difficulty, blue lips, or unresponsiveness. Seek same-day medical advice for new leg weakness, loss of bladder control or a sudden change in walking, which can indicate spinal cord compression, and tell any emergency team about the condition because airway management may be difficult.