How is Sly Syndrome diagnosed?

Sly syndrome, also known as mucopolysaccharidosis type VII (MPS VII), is a rare genetic disorder that affects the body's ability to break down certain complex sugars called glycosaminoglycans (GAGs). This leads to the accumulation of GAGs in various tissues and organs, causing a wide range of symptoms.

Diagnosing Sly syndrome involves a combination of clinical evaluation, laboratory tests, and genetic analysis. The process typically begins with a thorough medical history review and physical examination by a healthcare professional who specializes in genetic disorders.

Medical history review: The doctor will ask about the patient's symptoms, their onset, and their progression over time. They will also inquire about any family history of genetic disorders or consanguinity (when parents are closely related). This information helps in assessing the likelihood of Sly syndrome.

Physical examination: The doctor will perform a comprehensive physical examination to look for signs and symptoms associated with Sly syndrome. These may include facial abnormalities, skeletal deformities, enlarged liver or spleen, joint stiffness, and developmental delays.

Laboratory tests: Various laboratory tests are used to support the diagnosis of Sly syndrome. These may include:

• Urine tests: A urine sample is analyzed to measure the levels of GAGs. Elevated levels of GAGs can indicate the presence of Sly syndrome.


• Blood tests: Blood samples are examined to measure the activity of specific enzymes involved in GAG metabolism. Sly syndrome is characterized by deficient activity of the enzyme beta-glucuronidase.


• Enzyme analysis: In some cases, a skin biopsy or a small sample of cells from the patient's body may be taken to assess the activity of beta-glucuronidase directly.

Genetic analysis: Once the clinical and laboratory findings suggest a diagnosis of Sly syndrome, genetic testing is performed to confirm the presence of mutations in the GUSB gene. This gene provides instructions for producing the beta-glucuronidase enzyme. Genetic analysis can identify specific mutations that are known to cause Sly syndrome.

It is important to note that the diagnosis of Sly syndrome may require multiple tests and evaluations, and it should be carried out by healthcare professionals experienced in diagnosing and managing rare genetic disorders. Early diagnosis is crucial for implementing appropriate treatment strategies and providing necessary support to individuals and their families.