MPS IV Morquio

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 IV are either type A or B. Each type is missing or low in in a specific enzyme

• MPS IVA is missing or low in N-acetyl-galactosamine 6-sulfatase

• MPS IVB is missing or low in beta-galactosidase

These enzymes are essential in breaking down mucopolysaccharides keratan sulphate and chondroitin sulphate in type A and keratan sulphate in type B. When these mucopolysaccharides are not completely broken down they remain stored in the body. The symptoms of MPS IV are a result of the build-up of keratan sulphate and chondroitin sulphate in the body. Babies may show little sign of the disease but as more and more cells build up with partially broken down keratan sulphate and chondroitin sulphate symptoms start to appear.

MPS IV 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 in our publication.

For each pregnancy the chances of a baby inheriting MPS IV are completely independent of whether a previous child was affected with MPS IV. With each pregnancy there is a 1 in 4 chance that the baby will be affected by MPS IV.

All parents of children with MPS IV 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 IV, screening tests can be arranged early on during a pregnancy for those families who already have a child with MPS IV. 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 IV.

It might also be possible to have Pre-implantation genetic diagnosis (PGD) screening to avoid passing MPS IV 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.

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 that.

During a 10 year period (1989 to 1999) 26 babies were born with MPS IV in the UK.

It is important to note that people affected by either MPS IVA or MPS IVB may not experience all the symptoms. Where symptoms are present they vary in severity from one person to another. MPS IVA is more common than MPS IVB. Although clinical features are similar in both types they are usually milder in MPS IVB. In most cases people with MPS IV have normal intelligence.

For more on the symptoms, see:

• Appearance

• Dental

• Bones and joints

• Brain

• Ears

• Eyes

• Heart

• Liver, spleen and abdomen

• Lungs

Enzyme Replacement Therapy (ERT)

For people with MPS IVA ERT is a long-term therapy whereby the missing or deficient enzyme is given via an intravenous infusion. The name for the replacement enzyme in MPS IVA is elosulfase alfa and the brand name is Vimizim®. Vimizim® was licensed as an ERT in 2014 in the EU and approved for use in MPS IVA in the UK in 2015. The treatment has led to overall less physical deterioration leading to reduced disability and some people benefiting from increased energy levels. The treatment is unlikely to reduce certain complications, such as spinal cord damage.

Vimizim® is a weekly infusion lasting 4 to 5 hours that is usually administered at home. More information about Vimizim® can be found at www.vimizim.com and an EU version of the patient information leaflet is here. The Managed Access Agreement (MAA) guide for patient and parents is here.

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.

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.