What are the other Names for this Condition? (Also known as/Synonyms)

• MPS7
• Mucopolysaccharide Storage Disease Type VII
• Sly Syndrome

What is Mucopolysaccharidosis Type VII? (Definition/Background Information)

• Mucopolysaccharidosis Type VII (MPS VII or Sly Syndrome) is a rare, genetic metabolic condition that involves an inability of the body to breakdown glycosaminoglycans, which are long chains of sugar molecules. The condition is inherited in an autosomal recessive manner, meaning two copies (one from each parent) of the faulty gene are needed to cause signs and symptoms of the disorder
• The inheritance of the faulty genes prevents the body from producing an enzyme (known as the beta-D-glucuronidase enzyme) that is responsible for breaking down the sugar molecules. This inability to breakdown these sugars, causes it to buildup leading to many defects
• Since the condition is genetic, it is present at birth. Although, significant signs and symptoms of Mucopolysaccharidosis Type VII are mostly seen during childhood. Babies with severe MPS Type VII may die in utero or shortly after birth
• A healthcare professional can use various diagnostic tools, such as a physical exam, electrocardiogram, urinalysis (analysis of urine), and X-rays of the affected regions, to help diagnose Mucopolysaccharidosis Type VII
• There is no cure for Mucopolysaccharidosis Type VII; however, the treatment provided is symptomatic. These can include enzyme replacement, bone marrow transplant, and other organ-specific treatments
• The prognosis of Mucopolysaccharidosis Type VII depends upon the severity of the condition. Children with milder signs and symptoms have a better prognosis than those with severe MPS Type VII

Who gets Mucopolysaccharidosis Type VII? (Age and Sex Distribution)

• Mucopolysaccharidosis Type VII is a rare congenital disorder that is present at birth. In some cases, the signs and symptoms are not observed at birth, but during early childhood
• The incidence of the condition is around 1 in 250,000 newborns. It is one of the most rarest types of mucopolysaccharidosis
• This inherited genetic disorder can affect males and females of different races and ethnic backgrounds

What are the Risk Factors for Mucopolysaccharidosis Type VII? (Predisposing Factors)

• A genetic predisposition due to family history increases the risk for Mucopolysaccharidosis Type VII

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mucopolysaccharidosis Type VII? (Etiology)

• Mucopolysaccharidosis Type VII is caused by inheriting faulty genes that prevents the body from producing a certain enzyme, known as the beta-D-glucuronidase enzyme. The gene responsible for MPS VII is the GUSB gene. The condition is inherited in an autosomal recessive manner
• The enzyme is responsible for breaking down long chains of sugars, called glycosaminoglycans (GAGs). Due to a lack of production of this enzyme, GAG sugar molecules get abnormally accumulated in a structure called lysosome within the cells. The disorder is a kind of “lysosomal storage disease”, because the accumulation within special compartments of the cells, called lysosomes
• Lysosomes are a kind of recycling plant within the cells - they break down larger, more complex organic molecules into smaller molecules, which the cells can then reuse. When important enzymes are not functioning efficiently, the lysosomes become bloated and eventually, the cell gets ‘filled-up’ being unable to function anymore, leading to a disease state
• The complex molecules glycosaminoglycans used to be called “mucopolysaccharides”; the term “mucopolysaccharidosis” literally means an overabundance of mucopolysaccharides. Mucopolysaccharidosis Type 7 is also known as Sly Syndrome

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Mucopolysaccharidosis Type VII?

Mucopolysaccharidosis Type VII is a congenital disorder. If the condition is mild, then noticeable features of the disorder are not commonly present at birth. The onset of significant signs and symptoms occur during childhood. The severity of the condition varies from one child to another and it may be mild or severe.

The signs and symptoms of Mucopolysaccharidosis Type VII may include:

• Abnormally large head (macrocephaly) with abnormal facial features
• Presence of large tongue (macroglossia)
• Enlarged liver (hepatomegaly) and enlarged spleen (splenomegaly)
• Frequent respiratory infections due to narrowing of windpipe
• Frequent ear infection, hearing difficulties
• Sleep disorder such as sleep apnea
• Corneal clouding
• Bone and joint abnormalities
• Heart valve defects
• Stunted growth
• In some individuals, there is no decrease in mental cognition and the condition does not affect one’s IQ levels. However, in others, a declining intellectual ability is noted

In case of a very severe form of MPS Type VII, an excess buildup of fluid is observed in the fetus, while in the womb. This leads to a condition called hydrops fetalis. In such cases, most babies die shortly following birth or are stillborn.

How is Mucopolysaccharidosis Type VII Diagnosed?

Diagnostic tools used by a healthcare provider in the diagnosis of Mucopolysaccharidosis Type VII can include:

• Physical examination and analysis of previous medical history
• Peripheral smear exam may reveal abnormal lymphocytes containing cytoplasmic inclusions
• Urine tests: Increased levels of dermatan sulfate and heparin sulfate may be seen
• Hearing tests
• Sleep studies may be performed
• X-ray of different parts of the body may reveal bony abnormalities
• Electrocardiogram (EKG) to test the heart function
• Echocardiogram to determine heart defects
• MRI scan of brain to determine brain defects
• Genetic testing for changes in specific genes
• In many cases, the diagnosis is confirmed in the lab by a test called beta-D-glucuronidase enzyme assay, performed on fibroblast cells or leukocytes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mucopolysaccharidosis Type VII?

Complications of Mucopolysaccharidosis Type VII may include:

• Inguinal hernia causing a bulge on the side of the pubic bone, abdominal weakness, numbness in the groin, groin pain especially while coughing or lifting heavy objects
• Umbilical hernia causing an usually painless, soft bulge at the navel; the bulge is more visible when the baby cries or coughs
• Severe GI tract abnormalities
• Vision and hearing loss
• Carpal tunnel syndrome causing hand signs and symptoms such as radiating pain within the hand, tingling sensation and numbness, weakness in strength of hand muscles, etc.
• Short stature
• Frequent incidence of pneumonia
• Heart defects; congestive heart failure
• Fluid buildup in the brain (hydrocephalus)
• Decreased life span
• Hydrops fetalis, resulting in stillbirths or death of the infant immediately following its birth

How is Mucopolysaccharidosis Type VII Treated?

There is no cure for Mucopolysaccharidosis Type VII, since it is a genetic condition. Treatment for MPS Type VII is dependent on individual signs and symptoms and based on the organs that are affected. Since, this congenital condition involves various parts of the body and body systems, a team of healthcare professionals of diverse specialties are needed to manage MPS VII. An individualized treatment (case-by-case approach) is provided to improve the quality of life. This is also based on the specific set of signs and symptoms and complications that develop in each child/individual.

The treatment measures may include:

• Enzyme replacement therapy: Replacement of the missing enzyme to help in the breakdown of glycosoaminoglycans
• Bone marrow transplant
• Other organ specific treatments as specified by the healthcare provider including:
  • Orthopedic surgery for correcting bone and joint abnormalities
  • Hernia repair for inguinal and umbilical hernia
  • Corneal transplant for vision abnormalities
  • Tonsillectomy for frequent ear and throat infections
  • Correction of hearing defects
  • Surgical treatment for carpal tunnel syndrome
• For improving motor skills and mental disabilities, special therapeutic treatment (by physical and occupational therapists) and supportive care is required
• Research is being currently undertaken to treat Mucopolysaccharidosis Type VII using gene therapy

How can Mucopolysaccharidosis Type VII be Prevented?

• Currently, there are no specific methods or guidelines to prevent Mucopolysaccharidosis Type VII, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Mucopolysaccharidosis Type VII
• Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory

What is the Prognosis of Mucopolysaccharidosis Type VII? (Outcomes/Resolutions)

Mucopolysaccharidosis Type VII (Sly Syndrome) is a progressive disorder that has a generally poor prognosis. However, the prognosis also depends upon the severity of the signs and symptoms.

• Infants with very severe forms of MPS Type VII die in the womb, immediately following birth, or during infancy
• Children with severe signs and symptoms generally die during infancy or childhood
• Children with milder signs and symptoms are known to reach adolescence stage or even adulthood (early 20s)

Additional and Relevant Useful Information Mucopolysaccharidosis Type VII:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/