A new genetic test for newborns has been found to be successful in screening for rare genetic disorders, Prader Willi, Angelman and Dup15q syndromes.
It is hoped the test could open new avenues for earlier diagnosis and treatment, paving the way for the three chromosome 15 imprinting disorders to be added to newborn bloodspot screening programs (heel prick test) for the first time.
The research, led by Melbourne’s Murdoch Children’s Research Institute (MCRI), reported that screening for Prader Willi, Angelman and Dup15q syndromes using the new type of test was feasible, reliable and scalable.
The three disorders are characterised by varying degrees of intellectual disability, autism, behavioural problems, seizures and/or severe obesity. About 135 babies are born with one of these disorders each year in Australia, but the disorders are not included in newborn screening programs, and many go undiagnosed in the first year of life.
The study, published in The Journal of the American Medical Association Network Open, was the first to validate the use of a low-cost, specialised screening method called Methylation Specific-Quantitative Melt Analysis (MS-QMA), developed by MCRI researchers, for these disorders at a large scale.
The one-step test can be used to screen for the three conditions simultaneously, by looking at the number of chemical modifications or marks called methylation added to affected genes, which are not present at such high or low levels in children without these disorders.
MCRI Associate Professor David Godler said a key reason why these disorders were not included in current newborn screening programs was the lack of a test with low laboratory costs that could work at a population scale.
“Tests are currently only performed on those suspected of having these disorders, and only if features are recognised by a child’s doctor, and subsequently referred for appropriate testing,” he said. “This is not the case with newborn screening where testing is performed on all newborns before symptoms become apparent.”
The Victorian Government provided a $100,000 grant to MCRI as part of the 2018 Victorian Medical Research Acceleration Fund to support the development of the new screening method for the rare disorders.
The study first checked for accuracy, with the test correctly distinguishing most of the 167 samples from people who had one of the disorders. It was then tested on 16,579 newborns in Victoria with the test identifying two with Prader Willi, two with Angelman and one with Dup15q.
MCRI Professor David Amor said that if these findings were replicated in future independent studies, adding these chromosome 15 imprinting disorders to newborn screening programs would allow for earlier diagnosis and using targeted interventions as they emerge, such as gene therapy for Angelman syndrome.
“For Prader Willi, diagnosis in infancy allows for early initiation of growth hormone treatment to improve long term health outcomes,” he said.
“For Angelman and Dup15q, most infants do not receive an early diagnosis that would allow intervention in the first year of life. But such early diagnosis, if available through newborn screening, could prevent the diagnostic odyssey, reduce medical costs and the significant stress and anxiety currently experienced by the families while they await a diagnosis.”