It is not uncommon for a diagnosis of Tay-Sachs or Sandhoff disease to take some time to determine. This is often because early symptoms are non-specific, and more common disorders are thus first considered. In part a diagnosis relies upon knowledge that the diseases exist. In these cases, diagnosis can be confirmed in a timely manner.

Every family will experience a different diagnostic journey. In most cases, investigations are undertaken due to concerns regarding a child’s symptoms. However, in some cases, diagnostic tests are undertaken because of a family history of disease.

If your GP or paediatrician suspects one of the diseases, it is likely they will refer you to a specialist neurologist or metabolic doctor to undertake necessary diagnostic investigations.

Biochemical testing

Testing of your child or loved one’s beta-hexosaminidase A and beta-hexosaminidase B enzymatic activity is usually the first step in confirming a suspected diagnosis of Tay-Sachs or Sandhoff disease.

This test is typically performed from a blood sample, and may take some weeks to obtain a result.

In individuals with Tay-Sachs or Sandhoff disease, levels of enzyme activity are greatly reduced when compared to those without the diseases. This is considered a positive result and means it is highly likely that the disease is present in the individual.

It is possible that ‘borderline’ positive tests may result, in which case testing may be repeated, or additional tests such as genetic testing, may be performed.

Carriers can also be detected by enzyme testing. As they possess only one dysfunctional copy of the gene, they typically demonstrate 50% of the enzyme activity present within the general population. It is important to note that this amount of enzyme is sufficient for normal brain function, which is why disease carriers do not develop disease symptoms.

Genetic testing

After confirmation of decreased enzyme activity in an individual, the next step is to confirm the presence of diseases by examining the person’s DNA. This test looks to confirm the presence of the disease-causing mutations on both copies of the individual’s genes.

The DNA is usually obtained by taking a sample of blood, or of the cells lining the inside of their cheek.

Pre-conception and pre-natal screening

For those individuals whose heritage puts them at risk of being a carrier for the diseases, or for those with a known family history, screening before becoming pregnant or before giving birth may be considered to determine whether they are a carrier. This may be initiated by the individual, their GP or obstetrician.

Screening may be performed via biochemical and/or genetic testing, as described above, although examining the person’s DNA is more accurate.

In Australia, there are also some targeted screening programs in place that aim to identify the carrier status of members of Ashkenazi Jewish communities, in which Tay-Sachs disease is historically more common. However, it is important to note that Tay-Sachs and Sandhoff disease can affect people across many ethnicities.

There are reproductive options if you are a carrier and are planning a family. These options may be discussed with your genetic counsellor or obstetrician.

Mackenzie’s Mission

“Mackenzie’s Mission is a study providing reproductive genetic carrier screening to 10,000 Australian couples who are either planning to have children or are in early pregnancy.

The screening will give couples information about their likelihood of having a child with a severely debilitating and/or life-limiting genetic condition occurring in childhood.

Couples who take part in the study will be offered information and support to help them make informed choices about whether or not to have screening.

If couples choose to have the test, they will be screened for about 750 severe, childhood-onset genetic conditions, including conditions where early diagnosis and treatment can improve a child’s health.

Couples who have an increased chance of having a child with any of these genetic conditions will be supported and informed about their reproductive options, enabling them to make choices according to their own values.”

Tay-Sachs and Sandhoff diseases are amongst the genetic conditions screened for.

Importantly, the study will inform the future of pre-conception and prenatal screening for severely debilitating and/or life-limiting genetic conditions in Australia.

For further information on Mackenzie’s Mission, visit their website.