Blood test offers faster, less invasive diagnosis for rare genetic diseases in children and infants

Researchers from the University of Melbourne and Murdoch Children’s Research Institute (MCRI) have developed a blood test capable of rapidly diagnosing rare genetic diseases in babies and children, eliminating the need for costly and invasive procedures and giving families earlier access to treatment.

Genome sequencing has advanced the diagnosis of rare diseases, however this test is only successful in half of all cases. The remaining half of patients must undergo additional functional tests to confirm if a gene mutation is causing the disease. This diagnostic process can take months or years with no guarantee of a result, as most functional tests are only applicable to a single or handful of rare diseases.

Now new research, published in the journal Genome Medicine reveals a new blood test can rapidly detect abnormalities in up to 50% of all known rare genetic diseases in a matter of days by analyzing the pathogenicity of thousands of gene mutations at once, potentially replacing thousands of other functional tests.

University of Melbourne Associate Professor David Stroud said, “A disease is rare if it affects fewer than one in 2,000 people and there are more than 7,000 different rare diseases, most of which have a genetic origin and many of these diseases are serious and progressive.”

“If our blood test can provide clinical diagnoses for even half of the 50% of patients who don’t get a diagnosis through genome sequencing, that’s a significant outcome as it means those patients don’t have to undergo unnecessary and invasive testing such as muscle biopsies, which for a baby requires general anesthetic and that doesn’t come without risks.”

Murdoch Children’s Research Institute Professor David Thorburn said, “By providing patients and their families with a rapid clinical diagnosis, the patient has a greater chance at survival as they can begin treatment far sooner, if available.”

“Even in cases where a child has died from an undiagnosed genetic disease, this new test can be carried out on tissue samples to determine the genetic mutation responsible for their death. Such diagnoses not only provide closure to families, but this information can also be used in IVF to help the parents to have future children who have not inherited the life-threatening disease.”

The research team benchmarked their test against an existing clinically accredited enzyme test offered by the Victorian Clinical Genetics Services at MCRI, focussing on mitochondrial diseases. These are a group of severe rare disorders that rob the body’s cells of energy, causing single or multiple organ dysfunction or failure, and potentially death.

The team found, comparatively, their new test is more effective in confirming a mitochondrial disease diagnosis as it’s much more sensitive and accurate and can produce faster results.

University of Melbourne Dr. Daniella Hock said, “A recent health economics analysis in collaboration with the Melbourne School of Population and Global Health showed that our test could be offered at a similar cost to the enzyme test that is currently offered clinically for mitochondrial diseases, but our test is much more cost-effective as it can test for thousands of different genetic diseases, whereas other functional tests are mostly targeted to a small number of genetic disorders.”

Researchers are now in the process of recruiting 300 patients with a range of different genetic disorders to participate in a study to investigate the broad utility of their diagnostic test.

It’s anticipated the blood test will eventually be offered as a diagnostic service at the Victorian Clinical Genetic Services.

Researchers from the University of Melbourne and Murdoch Children’s Research Institute (MCRI) have developed a blood test capable of rapidly diagnosing rare genetic diseases in babies and children, eliminating the need for costly and invasive procedures and giving families earlier access to treatment.

Genome sequencing has advanced the diagnosis of rare diseases, however this test is only successful in half of all cases. The remaining half of patients must undergo additional functional tests to confirm if a gene mutation is causing the disease. This diagnostic process can take months or years with no guarantee of a result, as most functional tests are only applicable to a single or handful of rare diseases.

Now new research, published in the journal Genome Medicine reveals a new blood test can rapidly detect abnormalities in up to 50% of all known rare genetic diseases in a matter of days by analyzing the pathogenicity of thousands of gene mutations at once, potentially replacing thousands of other functional tests.

University of Melbourne Associate Professor David Stroud said, “A disease is rare if it affects fewer than one in 2,000 people and there are more than 7,000 different rare diseases, most of which have a genetic origin and many of these diseases are serious and progressive.”

“If our blood test can provide clinical diagnoses for even half of the 50% of patients who don’t get a diagnosis through genome sequencing, that’s a significant outcome as it means those patients don’t have to undergo unnecessary and invasive testing such as muscle biopsies, which for a baby requires general anesthetic and that doesn’t come without risks.”

Murdoch Children’s Research Institute Professor David Thorburn said, “By providing patients and their families with a rapid clinical diagnosis, the patient has a greater chance at survival as they can begin treatment far sooner, if available.”

“Even in cases where a child has died from an undiagnosed genetic disease, this new test can be carried out on tissue samples to determine the genetic mutation responsible for their death. Such diagnoses not only provide closure to families, but this information can also be used in IVF to help the parents to have future children who have not inherited the life-threatening disease.”

The research team benchmarked their test against an existing clinically accredited enzyme test offered by the Victorian Clinical Genetics Services at MCRI, focussing on mitochondrial diseases. These are a group of severe rare disorders that rob the body’s cells of energy, causing single or multiple organ dysfunction or failure, and potentially death.

The team found, comparatively, their new test is more effective in confirming a mitochondrial disease diagnosis as it’s much more sensitive and accurate and can produce faster results.

University of Melbourne Dr. Daniella Hock said, “A recent health economics analysis in collaboration with the Melbourne School of Population and Global Health showed that our test could be offered at a similar cost to the enzyme test that is currently offered clinically for mitochondrial diseases, but our test is much more cost-effective as it can test for thousands of different genetic diseases, whereas other functional tests are mostly targeted to a small number of genetic disorders.”

Researchers are now in the process of recruiting 300 patients with a range of different genetic disorders to participate in a study to investigate the broad utility of their diagnostic test.

It’s anticipated the blood test will eventually be offered as a diagnostic service at the Victorian Clinical Genetic Services.