MPS VII, Sly Disease
What else is it called?
- beta-glucuronidase deficiency
- GUSB deficiency
- MPS VII
- MPS disorder, type VII
- Mucopolysaccharidosis 7
- Mucopolysaccharidosis VII
- Sly Syndrome
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What causes it?
MPS VII is caused by mutations (changes) in the GUSB gene. This gene provides instructions for producing the enzyme beta-glucuronidase which plays a role in the breakdown of large sugar molecules called glycosaminoglycans (GAGs), originally known as mucopolysaccharides.
Mutations (changes) in the GUSB gene reduces or eliminates the function of beta-glucuronidase. The lack of beta-glucuronidase causes the build-up of GAGs within the cells, specifically the lysosomes. Lysosomes are sections in the cell that digest and recycle various molecules. The build-up of GAGs increases the size of the lysosomes, enlarging many tissues and organs.
How common is it?
The exact prevalence of MPS VII is unknown. However, it is estimated to affect 1 in 250,000 new-borns. MPS VII is one of the rarest types of mucopolysaccharidosis.
What are the signs and symptoms?
MPS VII is a progressive condition and affects most tissues and organs. The severity of MPS VII can vary greatly from patient to patient.
In the most severe cases, babies will suffer from hydrops fetalis. This is a condition where excess fluid builds up in the body before the baby is born. Most babies with hydrops fetalis are still born or die soon after birth.
Other individuals with MPS VII usually start showing signs and symptoms during early childhood. Signs and symptoms may include:
- Macrocephaly (a large head)
- Hydrocephalus (a build-up of fluid in the brain)
- Distinctive-looking facial features that are described as “coarse”
- Macroglossia (large tongue)
- Hepatosplenomegaly (enlarged liver and spleen)
- Heart valve abnormalities
- A soft out-pouching around the bellybutton (umbilical hernia)
- A soft out-pouching around the lower abdomen (inguinal hernia)
- Narrow airways
- Frequent upper respiratory infections
- Short pauses in breathing during sleep (sleep apnoea)
- Cloudy cornea (can cause significant vision loss)
- Recurrent ear infections
- Hearing loss
- Developmental delay and progressive intellectual disability (although intelligence is unaffected in some people with MPS VII)
As the patient gets older, there are various skeletal abnormalities that become more pronounced including:
- Short stature (height significantly shorter than average)
- Joint deformities that affect mobility
- Dysostosis multiplex (multiple skeletal abnormalities seen on X-ray)
- Carpal tunnel syndrome (numbness, tingling and weakness in the hands and fingers)
- Spinal stenosis (narrowing of the spinal canal in the neck which can damage the spinal cord)
The life expectancy of patients with MPS VII varies depending on the severity of the symptoms of the individual. Some patients do not survive past infancy whereas others may live into adolescence or adulthood. The most common causes of death in patients with MPS VII are heart disease and airway obstruction.
How is it diagnosed?
A diagnosis of this condition is made through clinical evaluation, detailed patient and family history and specialized tests. Tests include specialised blood and urine tests. Molecular genetic testing can confirm the diagnosis by showing mutations in the GUSB gene. Prenatal diagnosis is also possible by measuring beta-glucuronidase activity.
Can it be treated?
In 2017 Mepsevii, an enzyme replacement therapy was approved at treatment for children and adults with MPS VII.
Other treatment is symptomatic and supportive. Surgery may be necessary for bone deformities, hernias or cardiovascular abnormalities.
Individuals with MSP VII may be sensitive to anaesthesia due to malformations in the airway or cervical spine. Therefore, extra precautions should be taken before surgery.
Do my family need to be tested?
MPS VII is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.
The pattern of inheritance of MPS VII is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with MPS VII are carriers.
When both parents are carriers, the risk to the baby in each pregnancy is
- 25% chance (1 in 4) of developing the condition
- 50% chance (1 in 2) for the baby to be a carrier of the condition
- 25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier
Genetic counselling can be requested to get a full explanation.