MPS III Sanfilippo
What causes MPS III?
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 disease but as more and more cells build-up of partially broken down heparan sulphate symptoms start to appear.
How is MPS III inherited?
MPS III is an autosomal recessive disease this means that both parents must carry the same affected gene and each pass this same affected gene to their child.
People probably carry from 5 to 10 genes with mutations in each of their cells. Problems happen when the particular gene is dominant or when a mutation is present in both copies of a recessive gene pair. Genes are the unique set of instructions inside our bodies that make each of us an individual. They are the blueprint for our growth and development, as well as controlling how our bodies function. Genes are carried on structures called chromosomes and it is usual to have 23 pairs. A child will inherit half of the chromosomes from the mother and the other half from the father resulting in 23 pairs. 22 of these pairs look the same in both males and females. Pair 23 are the sex chromosomes, and this is the pair that differ between females and males. The X chromosome is inherited from the mother and the Y chromosome is inherited from the father. More information about inheritance is available here.
For each pregnancy the chances of a baby inheriting MPS III are completely independent of whether a previous child was affected with MPS III. With each pregnancy there is a 1 in 4 chance that the baby will be affected by MPS III.
All parents of children with MPS III can benefit from genetic counselling, the counsellor can provide advice on the risk to close relatives and to suggest whether the wider family should be informed. To find out during a pregnancy, if the baby is affected by MPS III, screening tests can be arranged early on during a pregnancy for those families who already have a child with MPS III. Where only one parent is a carrier, they can opt for carrier screening but it is not 100% reliable or accurate and is not possible in all cases. Amniocentesis and chorionic villus sampling are both available during the pregnancy to find out if the baby is affected by MPS III.
It might also be possible to have Pre-implantation genetic diagnosis (PGD) screening to avoid passing MPS III to the baby. PGD is an assisted fertility treatment that involves checking the chromosomes of embryos before they are transferred in the womb using IVF techniques.
How common is MPS III?
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.
How are people with MPS III affected?
MPS III causes progressive intellectual disability and loss of mobility in children, there is little clinical difference between the different types of MPS III disease. The disease will affect children differently and its progress can be much faster and in some cases more than others. Life expectancy in MPS III is extremely varied, most people with MPS III live into their teenage years, and some live longer, into their twenties or thirties.
The disease tends to progress through the following stages:
- The first stage during pre-school years when diagnosis is usually established. Symptoms are commonly seen in all children such as diarrhoea, frequent respiratory and ear infections as well as overexcited behaviour making diagnosis challenging.
The second stage is characterised by extremely active, restless and often very difficult behaviour. Language and understanding will gradually be lost and parents may find it hard not being able to have a conversation with their child. Some children never become toilet trained and those who do will eventually lose this ability.
The third stage is when children gradually lose skills and abilities they may have had previously, including speech, walking and the ability to eat.
For more information about the specific symptoms click through each of the symptom links below
Treatment options for people with MPS III
There is no cure for MPS III and no current approved treatment, treatment focuses on easing symptoms and giving the child the best quality of life for as long as possible.
MPS III mainly affects the brain and for any treatment to be effective it must reach the brain. Most drug treatments are blocked from reaching the brain by the blood brain barrier. This barrier separates the blood from the brain but does allow some materials to cross. Various Enzyme Replacement Therapies (ERTs) are currently in development including intrathecal enzyme therapy. Treatments for MPS III where research is ongoing include bone marrow transplants, gene therapy (using genes to treat or prevent disease) and chaperone therapy (a new approach aiming to bind and stabilise the affected enzymes).
More information on supportive care treatments for people with MPS III disease can be found in the treatments section.
Research and clinical trials for people with MPS III
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.
Living with MPS III
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 offers 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 and includes an Advocacy Officer based at Belfast City Hospital supporting members in Northern Ireland.
Get involved and support us in the community, volunteer or support fundraising; we are a small charity but with your support we can continue to offer a highly valued and essential service.
What is MPS III
MPS III, known as Sanfilippo disease, is one of the mucopolysaccharide storage diseases. MPS III was first identified by Dr Sanfilippo in 1963 and includes 4 different types A, B, C and D.
Our support line is open 9-5pm
Monday-Friday: 0345 389 9901
Out of hours line: open 5pm-10pm Monday-Friday and weekends:
07712 653 258
Royal Manchester Children’s Hospital (RMCH) has opened a stem cell gene therapy bone marrow transplant for MPSIIIA (Sanfilippo Syndrome). The trial is open to children with a predicted severe illness course (family history and/or genetic diagnosis) and aged under 2 years. We are open to patients from anywhere in the world, and treatment, travel and accommodation costs are met by the trial.