MPS III Sanfilippo

Mucopolysaccharides are long chains of sugar molecules used in the building of bones, cartilage, skin, tendons and many other tissues in the body. “Muco” refers to the thick jelly-like consistency of the sugar molecules, “poly” means many, and “saccharide” is a general term for the sugar part of the molecule. In the course of normal life there is a continuous recycling process of building new mucopolysaccharides and breaking down old ones. The breakdown and recycling process requires a series of special biochemical tools called enzymes.

People with MPS III are either type A, B, C or D. Each type is missing or low in a specific enzyme

• MPS III A is caused by missing or altered heparan N sulphatase

• MPS III B is caused by missing or low in alpha-Nacetylglucosaminidase

• MPS III C is caused by missing or altered acetyl-CoAlpha-glucosaminide acetyltransferase

• MPS III D is caused by missing or low in N-acetylglucosamine-6-sulphatase

These enzymes are essential in breaking down mucopolysaccharides heparan sulphate. When heparan sulphate is not completely broken down it remains stored in the body. The symptoms of MPS III are a result of the build-up of heparan sulphate in the body. Babies may show little sign of the condition but as more and more cells build up with partially broken down heparan sulphate symptoms start to appear.

We have thousands of genes, and they are the blueprint for our growth and development, as well as controlling how our bodies function. If a particular gene is altered, then it may not work efficiently.

Genes are carried on structures called chromosomes. It is usual to have 23 pairs of chromosomes that are numbered in pairs from pair 1 to pair 22, plus one pair of sex chromosomes: XX for a female and XY for a male.

Each gene is a template for making a protein needed for the body to function. A child will inherit one set of chromosomes from their mother in the egg, and one set from their father in the sperm. Therefore, we each have two copies of each gene, one of which is inherited from each parent.

In a person with MPS III, both copies of the associated gene have genetic alterations (mutations). This is an autosomal recessive inheritance pattern. Both parents each carry one copy of the altered gene, but they do not show signs and symptoms of the disease. This is known as being a carrier. Brothers and sisters of a person affected by MPS III might also be carriers of the condition and they may wish to be referred to their local genetic department about the potential risks in future pregnancies.

Genetic counselling

MPS III is a genetically inherited condition and there is a risk of recurrence in future pregnancies for a couple with an affected child. Therefore, parents of children with MPS III should be referred to a genetic counsellor. The counsellor will provide non-directive advice on reproductive choices, the risk to close relatives, and will suggest whether the wider family should be informed. In order to access genetic counselling, you can request a referral from either your specialist centre or your GP. Genetic services are provided by regional genetic centres.

More information about inheritance is available in our publication.

Testing for MPS III Sanfilippo in pregnancy

It is important to contact your doctor if you are planning to become pregnant, or as soon as you suspect that you may be pregnant, if you wish to discuss your family history and options. Both amniocentesis and chorionic villus sampling can be used to diagnose MPS III during pregnancy.

Amniocentesis involves using a needle to take a sample of fluid from around your baby. This fluid is then used to test the baby’s DNA for genetic alterations in your family. Chorionic villus sampling is similar to amniocentesis but instead involves testing a sample of cells from where the placenta attaches to the uterus.

Pre-implantation genetic testing (PGT) is an assisted fertility treatment. It may be possible to have PGT to avoid passing MPS III to the baby if you and your partner are known to be carriers of the condition. PGT involves checking the chromosomes of embryos for gene alterations before they are implanted in the womb, using IVF techniques. This is a complex process and requires referral from your regional genetics service.

It is estimated that nearly 6% of the UK population (around 3.5million people) will be affected by a rare disease at some point in their lives. A single rare disease may affect up to about 30,000 people however the vast majority of rare diseases affect far fewer than.

During a 10 year period (1988 to 1998) 97 babies were born with MPS III in the UK.

From 2010 to 2020, 83 babies were born with MPS III in the UK.

It is important to note that people affected by MPS III may not experience all the potential symptoms and severity can vary from one person to another. The progression of MPS III is also variable, however, to help understand the condition it is described in three broad stages.

• First stage: In early childhood (age 1-4 years) parents may notice some delays in their child’s development, e.g. delayed speech and language (often put down to glue ear), delays in crawling or walking, hyperactive behaviour and sleeplessness. Autistic traits are often reported as well as challenging behaviours. Other signs can be very subtle and are often associated with common childhood illnesses, e.g. frequent cold-like symptoms and diarrhoea.

• Second stage: As your child gets older the physical features of MPS III may become more noticeable. Hyperactivity and challenging behaviours typically escalate and become more difficult to manage. Over time certain skills and abilities are gradually lost. They will begin to slow down, become more unsteady on their feet and tire more quickly. They may lose the ability to use words. Your child may show signs of difficulty when eating and drinking, with increased coughing and risk of choking.

• Third stage: There is a further neurological decline, with the loss of skills and abilities; mobility will be lost, with reliance on mobility aids and supportive equipment. The loss of mobility is often accompanied by a deterioration in the ability to eat and drink safely. Care turns more towards managing health needs and symptom management. MPS III Sanfilippo is a life-limiting condition; life expectancy is extremely varied.

For more on the symptoms, see:

• Appearance

• Dental

• Bones and joints

• Brain

• Ears

• Eyes

• Heart

• Liver, spleen and abdomen

• Lungs

At present there is treatment for symptoms as they arise, but no cure for the underlying disease. More information on supportive care treatments for people with MPS and related diseases can be found in the treatments section.

For an up-to-date list of current UK based trials taking place visit Be Part of Research (resource provided by the National Institute for Health Research). For an international search visit Clinical Trials (resource provided by the U.S. National Library of Medicine).

This resource provides information on trial status including recruiting, completed or withdrawn and worldwide trial locations. To find out more about past or current trials speak to your doctor and learn about the risks and potential benefits.

The MPS Society is the only UK charity at the forefront of supporting people and families affected by MPS and related diseases. Our extensive support services offer you a wide range of support and resources.

The team can advise and sign post you to adequate needs-led support and services in your local area as well as social care, home adaptions, education and much more.

The support team can visit you in your home and provide you with vital support.

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