MPS VII - Sly disease

What causes MPS VII?


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 VII are missing or are low in an enzyme called beta-glucuronidase which is essential in breaking down 3 mucopolysaccharides dermatan sulphate, heparan sulphate and chondroitin sulphate. When mucopolysaccharides are not completely broken down they remain stored in the body. The symptoms of MPS VII are a result of the build-up of dermatan sulphate, heparan sulphate and chondroitin sulphate in the tissues in the body. Babies may show little sign of the disease but as more and more cells build-up of partially broken down dermatan sulphate, heparan sulphate and chondroitin sulphate, symptoms start to appear.




How is MPS VII inherited?


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

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

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


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 this.

In the UK, MPS VII is the rarest mucopolysaccharidosis with an average of only one baby every 10 years born with the disease.




How are people with MPS VII affected?


MPS VII is immensely variable, in its most extreme form babies are born with a condition called hydrops fetalis. This is a very severe condition in which the baby retains an enormous amount of fluid throughout its body. Babies with hydrops fetalis rarely survive beyond a few weeks to a few months of age. Across the spectrum, some people with MPS VII have milder physical problems and learning disabilities while others have more severe physical problems and normal intelligence. For more information about the specific symptoms click through each of the symptom links below.




Treatment options for people with MPS VII


Enzyme Replacement Therapy (ERT)

For people with MPS VII 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 VII is vestronidase alfa-vjbk and the brand name is MEPSEVII®. MEPSEVII® received FDA approval in November 2017.

MEPSEVII® it is a fortnightly intravenous infusion lasting 4 hours. More information about MEPSEVII® can be found at www.mepsevii.com.

Haematopoietic Stem Cell Transplantation (HSCT)

Use of HSCT for MPS VII is limited by the rarity of the disease and tendency toward stillbirths. In certain circumstances, MPS VII can be effectively treated by HSCT provided that the developmental and clinical condition is good at the time of HSCT.

More information on these and supportive care treatments for people with MPS diseases can be found in the treatments section.




Research and clinical trials for people with MPS VII


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 VII


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 VII


MPS VII, known as Sly disease, is one of the mucopolysaccharide storage diseases. MPS VII was first identified by Dr Sly in 1972 and includes a spectrum of symptoms from mild to severe.

What causes MPS VII?


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 VII are missing or are low in an enzyme called beta-glucuronidase which is essential in breaking down 3 mucopolysaccharides dermatan sulphate, heparan sulphate and chondroitin sulphate. When mucopolysaccharides are not completely broken down they remain stored in the body. The symptoms of MPS VII are a result of the build-up of dermatan sulphate, heparan sulphate and chondroitin sulphate in the tissues in the body. Babies may show little sign of the disease but as more and more cells build-up of partially broken down dermatan sulphate, heparan sulphate and chondroitin sulphate, symptoms start to appear.




How is MPS VII inherited?


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

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

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


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 this.

In the UK, MPS VII is the rarest mucopolysaccharidosis with an average of only one baby every 10 years born with the disease.




How are people with MPS VII affected?


MPS VII is immensely variable, in its most extreme form babies are born with a condition called hydrops fetalis. This is a very severe condition in which the baby retains an enormous amount of fluid throughout its body. Babies with hydrops fetalis rarely survive beyond a few weeks to a few months of age. Across the spectrum, some people with MPS VII have milder physical problems and learning disabilities while others have more severe physical problems and normal intelligence. For more information about the specific symptoms click through each of the symptom links below.




Treatment options for people with MPS VII


Enzyme Replacement Therapy (ERT)

For people with MPS VII 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 VII is vestronidase alfa-vjbk and the brand name is MEPSEVII®. MEPSEVII® received FDA approval in November 2017.

MEPSEVII® it is a fortnightly intravenous infusion lasting 4 hours. More information about MEPSEVII® can be found at www.mepsevii.com.

Haematopoietic Stem Cell Transplantation (HSCT)

Use of HSCT for MPS VII is limited by the rarity of the disease and tendency toward stillbirths. In certain circumstances, MPS VII can be effectively treated by HSCT provided that the developmental and clinical condition is good at the time of HSCT.

More information on these and supportive care treatments for people with MPS diseases can be found in the treatments section.




Research and clinical trials for people with MPS VII


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 VII


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.





Useful links

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For treatment options

For research and clinical trials

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