New blood test screens for thousands of rare inherited diseases at once

Yahoo

25-05-2025

ST. PAUL, Minn., May 25 (UPI) -- A new rapid blood test for newborns could potentially detect genetic mutations linked to thousands of rare diseases all at once, greatly improving on current inefficient detection methods, according to a study to be presented Monday.
The new test developed by Australian scientists has proven highly accurate in identifying gene mutations associated with many rare, inherited diseases, all from just a minimally invasive blood sample taken from infants and children, the authors say.
The study, being unveiled at the European Human Genetics Conference in Milan, Italy, demonstrated that a single, untargeted test capable of analyzing 8,000 human proteins at once was able to correctly identify 83% of people with confirmed rare, inherited diseases.
The "proteomics" test was also able to differentiate between parental carriers of the mutations, who only have one copy of the defective gene, and the affected child, who carries two copies.
Those encouraging results are raising hopes for a new era in which screening infants and children for suspected inherited rare diseases can be accomplished quickly and efficiently for the first time, and that testing can be extended to many more of the estimated 300 million people worldwide affected by these genetic mutations.
Testing for suspected inherited diseases has traditionally been a time-consuming, costly and sometimes painful process that required different procedures for different suspected mutations. But that paradigm could be about to change, the study's lead author says.
Daniella Hock, a senior postdoctoral researcher at the University of Melbourne, told UPI that if the test is implemented in clinical labs, "it can potentially replace multiple functional tests. This can potentially reduce the diagnostic time for patients and families and healthcare costs.
"The test only requires only 1 milliliter of blood from infants, and results can be achieved in less than three days for urgent cases," she said.
One area in which the new proteomics test could have immediate benefits is in the battle against mitochondrial diseases, which are defined by the Cleveland Clinic as a group of genetic conditions that affect how mitochondria in human cells produce energy. Mitochondrial diseases render cells unable to produce enough energy, which can lead to life-threatening complications.
About 1 in 5,000 people worldwide have a mitochondrial disorder. Examples of such illnesses are Leigh's syndrome, which primarily affects the nervous system; Kearns-Sayre syndrome, which primarily affects the eyes and heart; and Leber hereditary optic neuropathy, which can cause a sufferer to quickly and unexpectedly lose their vision.
Hock said the current "gold standard" for screening for these rare maladies starts with genetic testing -- either whole exome or whole genome sequencing -- that currently provides a diagnosis to about half of patients.
"The remaining half often endure years of functional testing trying to identify which genetic change, that is, genetic variant, is causing the disease," she said, adding that more than 7,000 types of disease caused by mutations exist in more than 5,000 known genes.
Some of these current tests are invasive, requiring skeletal muscle or liver biopsies, and are often targeted to a single disease or a few diseases.
"If we take the example of mitochondrial disease, which is a type of rare disease that can be caused by over 350 different genes, the current clinical test to confirm mitochondrial disease is called respiratory chain enzymology," she said. "This enzyme test typically requires a skeletal muscle or skin biopsy and has a turnaround time of a few weeks."
The new proteomic test, which sequences proteins rather than genes, can reduce invasiveness and time to a diagnosis compared to other kinds of current clinical functional tests, its developers say.
"For about half of the individuals where DNA sequencing results are inconclusive, typically due to the identification of variants of uncertain significance, this single test can potentially be used to provide functional evidence to these genetic variants," Hock said.
Study co-author David Thorburn, one of Australia's foremost experts on genetics and co-group leader for brain and mitochondrial research at Murdoch Children's Research Institute in Melbourne, said the current process for determining if a child has one of the many possible genetic variances is a daunting one.
While there are many hundreds of different functional tests tailored to specific genes, "relatively few of these are available in clinical labs, so it is often a matter of contacting researchers who work on that gene, of which there may only be one or a handful internationally to see if they can assist," he told UPI in emailed comments.
"That often requires paperwork like material transfer agreements to be put in place, shipping costs of hundreds or even thousands of dollars if dry ice shipment is needed and frequently a timeframe of months to multiple years depending on whether they have a student or staff to do testing in a research context, where the rigor of the test may be variable," he added.
Thorburn said the new proteomics test, however, "provides a single pipeline that can potentially provide that evidence for about half the known rare disease genes and we are working hard to move it into a clinical test in Melbourne at our Victorian Clinical Genetics Services and working with expert clinical labs in the U.K., U.S.A. and elsewhere to support them doing that."
Having the test available clinically "could allow hundreds of families each year in Australia alone to get confirmed genetic diagnoses, so potentially thousands per year in the U.S.," he said. "For urgent cases, [for example], kids in ICU this can be done in as few as three days from sample receipt."
For those many thousands of patients, the new test could mean their "diagnostic odyssey is ended, unnecessary investigations are no longer needed, targeted therapies may be available, patients may qualify for a clinical trial and parents can be offered reproductive options," he said.