About MPS
MPS VII - Sly Disease
This information has been developed by the MPS Society of Australia to provide information about mucopolysaccharidosis type VII (MPS VII), its clinical presentation and medical management.
This content draws on the experiences of parents and doctors with reference to the medical literature. It is not intended to replace medical advice or care. For reference purposes, it may be useful to provide a copy of this information sheet to your GP and others who are involved in providing medical or supportive care.
WHAT IS MPS VII?
MPS VII, also known as Sly syndrome, is a rare inherited lysosomal storage disorder and one of the least common forms of mucopolysaccharidosis. It is caused by changes in the GUSB gene, which provides instructions for making the enzyme beta-glucuronidase. This enzyme is needed to break down certain glycosaminoglycans (GAGs), including dermatan sulfate, heparan sulfate and chondroitin sulfate.
When beta-glucuronidase is missing or does not work properly, these GAGs are not broken down normally and gradually accumulate inside cells. This can affect many different tissues and organs throughout the body. MPS VII has a very broad range of severity, and not everyone will experience the same combination or degree of symptoms.
HOW IS MPS VII INHERITED?
MPS VII is inherited in an autosomal recessive pattern. A person affected by MPS VII has changes in both copies of the GUSB gene, with one altered copy inherited from each parent. Parents who carry one altered copy generally do not have symptoms of the condition.
When both parents are carriers, each pregnancy has a 25% chance of resulting in a child with MPS VII, a 50% chance of the child being an unaffected carrier, and a 25% chance of inheriting neither altered copy. Genetic counselling can help families understand these risks and discuss testing options.
SIGNS AND SYMPTOMS
MPS VII can affect many parts of the body, and symptoms can range from very severe to relatively mild. In some babies, the condition may be apparent before or shortly after birth. Severe cases can include hydrops fetalis, where abnormal amounts of fluid accumulate in the developing baby.
Skeletal problems are common and may include short stature, joint stiffness, hip abnormalities, knock knees and curvature of the spine. The bones of the neck and upper spine can be particularly important because abnormalities may cause instability or place pressure on the spinal cord. Some people may develop weakness, changes in walking, pain or reduced mobility as the condition progresses.
MPS VII can also affect the heart, lungs and airways, hearing, vision and digestive system. Enlargement of the liver and spleen may cause abdominal enlargement and can sometimes affect eating or breathing. Respiratory problems can include recurrent chest infections, narrowing of the airways and sleep apnoea. Hearing loss and corneal clouding are also common. People with more severe forms may experience developmental delay or intellectual disability, while the degree of neurological involvement varies considerably between individuals.
DIAGNOSIS
Because MPS VII is extremely rare and its symptoms can overlap with other conditions, diagnosis may take time. Doctors may consider MPS VII when a person has a combination of characteristic skeletal, respiratory, organ or developmental features.
Testing generally involves looking for increased GAGs in the urine, followed by testing for reduced beta-glucuronidase enzyme activity. Genetic testing can then identify changes in the GUSB gene and help confirm the diagnosis. Early diagnosis can help families access appropriate specialist care and establish monitoring for complications.
MANAGING MPS VII
There is no single treatment that addresses every aspect of MPS VII. Care is usually coordinated by a multidisciplinary team, with treatment tailored to the individual’s symptoms and needs.
Regular monitoring may include assessment of the spine and joints, heart and lung function, hearing and vision. Physiotherapy and other therapies can help maintain movement and function, while orthopaedic or neurosurgical treatment may be required for significant skeletal or spinal problems. Respiratory support may be needed for sleep apnoea or other breathing difficulties, and hearing aids or other hearing support can assist with communication. Dental care, nutritional support and appropriate management of pain and gastrointestinal problems are also important.
TREATMENT
There is currently no cure for MPS VII. Treatment is focused on reducing the effects of the disease, maintaining physical function and managing complications. Enzyme replacement therapy (ERT) is available for MPS VII and uses a manufactured form of the missing enzyme, beta-glucuronidase, to help the body break down accumulated glycosaminoglycans (GAGs). ERT is given by intravenous infusion and is intended to improve or stabilise some of the physical effects of the disease.
Vestronidase alfa (Mepsevii) is an enzyme replacement therapy specifically developed for MPS VII. It has been approved in some countries for the treatment of MPS VII and may provide benefits for some non-neurological aspects of the disease. However, ERT does not correct the underlying genetic cause of MPS VII and may not reach all affected tissues, particularly the brain and areas of established skeletal disease. People receiving ERT may therefore continue to require monitoring and treatment for other complications.
In Australia, MPS VII and vestronidase alfa are not currently listed under the Life Saving Drugs Program (LSDP). The current Australian LSDP provides subsidised access to medicines for MPS I, MPS II, MPS IVA and MPS VI, but does not currently include MPS VII. This means that Mepsevii is not currently available through the LSDP for eligible Australian patients.
LIVING WITH MPS VII
The impact of MPS VII is different for every individual. Some people have significant medical and physical needs from early childhood, while others have a milder form and may live into adulthood. Ongoing medical care, appropriate therapies and practical support can help people manage symptoms and maintain their independence and quality of life.
Because MPS VII can affect many different parts of the body, coordinated care and communication between specialists is particularly important. With the right support, families and individuals can better understand the condition, plan for changing needs and make informed decisions about their care.
