While there are no formal criteria to enable a diagnosis of Sanfilippo syndrome, several types of tests are available for identifying the genetic disorder.
In Sanfilippo, the body cannot break down a large sugar molecule called heparan sulfate. Its resulting buildup leads to progressive intellectual disability and the loss of previously acquired skills.
The earlier the diagnosis, the more quickly patients and caregivers can seek support services and access to clinical trials, if desired.
Urine tests can measure the levels of heparan sulfate and other similar sugar molecules in the urine. If the levels of heparan sulfate are higher than normal, this can indicate Sanfilippo syndrome.
Although this test is non-invasive, it is not very accurate. So, it can be a useful first-line test. However, a negative urine test does not mean that the patient does not have Sanfilippo.
Blood tests are the gold standard for diagnosing Sanfilippo syndrome. They measure the activity of the enzymes that normally break down heparan sulfate in the blood. If one of these enzymes has little or no activity, a diagnosis can be established.
Typically these tests use blood drawn from the arm, which can be done at a doctor’s office or in a lab setting. This type of test is generally done as a follow-up after urine testing.
The activity of these enzymes also can be assessed using cell samples from blood or skin.
Genetic testing and newborn screening
Genetic testing involves looking for specific mutations that are known to cause Sanfilippo syndrome. Mutations in four genes — SGSH, NAGLU, HGSNAT, and GNS — cause Sanfilippo type A, B, C, and D, respectively. Identifying a mutation in one of these genes allows for a conclusive diagnosis.
Cells from a sample of blood, saliva, or a cheek swab are usually used in such genetic testing.
In recent years, there has been increasing interest in newborn screening. This involves doing genetic tests on newborns to diagnose a disease before symptoms appear. A positive finding allows treatment to start immediately. However, at present, Sanfilippo syndrome is not part of any newborn screening public health program in the U.S.