Mucopolysaccharidosis type III (Sanfilippo syndrome)

MPS III was first identified by Dr Sanfilippo in 1963. Four types exist depending on which enzyme is missing or altered. Type A involves heparan N-sulphatase, type B alpha-N-acetylglucosaminidase, type C acetyl-CoA alpha-glucosaminide acetyltransferase and type D N-acetylglucosamine-6-sulphatase. All four are needed to break down the sugar heparan sulphate, which stays stored in cells when the process fails.

Unlike MPS I, II and IV, the body-wide structural features are usually modest. Children are generally of normal weight and height at birth and in early childhood, then growth slows and adults tend to be shorter than expected from their parents. The main burden falls on the nervous system, which is why the condition is sometimes described by families as a form of childhood dementia.

The progression is variable, but it is helpful to describe three stages. In the first stage, between about 1 and 4 years, parents may notice delayed speech and language that is often attributed to glue ear, late crawling or walking, hyperactive behaviour and sleeplessness. Autistic traits and challenging behaviour are often reported. Other signs, such as frequent colds and diarrhoea, are subtle and look like common childhood illness.

In the second stage physical features become more apparent. Hyperactivity and challenging behaviour typically escalate and become harder to manage. Skills are gradually lost: a child slows down, becomes unsteady, tires more quickly and may lose words. Eating and drinking become harder, with increased coughing and a risk of choking.

In the third stage there is further neurological decline, mobility is lost and mobility aids and supportive equipment are needed. The ability to eat and drink safely deteriorates and care focuses on health needs and symptom management.

Bone and joint problems progress alongside the neurological decline. Curvature of the spine, both kyphosis and scoliosis, can develop, and large joints such as shoulders, elbows, hips and knees lose some movement. Many children stand and walk with knees and hips flexed on broad feet, and the fingers can curl.

Because balance and then walking are progressively lost, referral for occupational therapy, physiotherapy and hydrotherapy is recommended to protect comfort and everyday function. The MPS Society publishes a guide on how physiotherapy helps in MPS III.

Many children are first seen for developmental concerns, and the diagnosis can take time because early signs overlap with speech delay, autism and behavioural conditions. A specialist metabolic service can test urine for heparan sulphate and measure enzyme activity, and genetic testing identifies the type. Some families report being diagnosed only after a child became very unwell.

MPS III is inherited, so parents should be referred to a genetic counsellor who gives non-directive advice about future pregnancies and relatives. Referral can come from the specialist centre or GP, and services are provided by regional genetics centres. Amniocentesis and chorionic villus sampling can diagnose MPS III in pregnancy, and pre-implantation genetic testing may be possible for known carriers.

At present, treatment responds to symptoms as they arise. Sleep difficulty, seizures, reflux and constipation, behaviour that puts a child at risk, swallowing problems and pain each need their own plan, usually coordinated by a paediatrician or community team working with the specialist centre. The MPS Society reports a study of gastrointestinal disease in MPS III, reflecting how common bowel problems are.

The MPS Society also highlights the family impact. Qualitative research it lists describes the social and financial strain of MPS III across the stages. Short breaks, children's hospice services, specialist equipment and a social care assessment are part of a realistic care plan. Families can ask for an education, health and care plan and a continuing care assessment.

The MPS Society reports that in 2026 the US Food and Drug Administration approved a treatment called UX111 for the neurologic manifestations of MPS IIIA in children with preserved neurodevelopmental function, and that clinical research in MPS III is moving fast internationally. The charity stresses that this approval applies only in the United States and does not automatically mean the therapy will be available in the UK, where a separate evaluation and a NICE review are needed before access can be considered. Trials are listed on the National Institute for Health and Care Research Be Part of Research service, and the specialist team can advise on eligibility.

Call 999 for a seizure that does not stop within the time a care plan specifies, choking that does not clear, or breathing difficulty. Contact the child's team the same day for fever with poor feeding, persistent vomiting, a fall with a suspected fracture, or sudden changes in behaviour or alertness.