Rare disorders caught in new test
The ‘heel prick test’ for babies could soon be used to spot three rare genetic disorders.
Experts at the Murdoch Children’s Research Institute (MCRI) have developed a new test to screen for Prader Willi, Angelman and Dup15q syndromes.
They say it could open new avenues for earlier diagnosis and treatment, paving the way for the three disorders to be added to newborn bloodspot screening programs (heel prick tests).
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.
There has not been a test available for these three conditions with low laboratory costs that could work at a population scale, until now.
MCRI researchers have come up with a specialised screening method called Methylation Specific-Quantitative Melt Analysis (MS-QMA), that can be used to spot 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.
More recent research has shown that MS-QMA is feasible, reliable and scalable enough to be rolled out widely.
“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,” MCRI Associate Professor David Godler says.
“This is not the case with newborn screening where testing is performed on all newborns before symptoms become apparent.”
His new study finds that the cost, disorder prevalence and accuracy of MS-QMA as a first-tier test is in line with other conditions currently included in newborn screening programs.
“Having a high positive predictive value is important for newborn screening as it ensures that there is lower number of false positive results that need to be repeated, leading to lower overall laboratory costs, less work for maternity services in obtaining a repeated blood sample and minimises the psychological effect on families,” Associate Professor Godler said.
Adding tests for these 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,” MCRI Professor David Amor 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.”
The latest study is accessible here.