Newborn screening for spinal muscular atrophy

Testing in the newborn period is more effective than conventional clinical diagnosis pathways for improving health outcomes in infants with the rare genetic disease spinal muscular atrophy.

Children with spinal muscular atrophy (SMA) are more likely to walk, be more functionally independent and free of respiratory and feeding support when screened, diagnosed and treated shortly after birth, according to a new study conducted at Sydney Children’s Hospitals Network (SCHN) by UNSW Sydney researchers.

Significantly, the findings show newborn bloodspot screening (NBS) for SMA, coupled with potential to access disease-modifying therapies, is correlated with greater motor milestone acquisition with those diagnosed before the onset of symptoms reaching regular childhood developmental milestones.

The study, published in The Lancet Child & Adolescent Health, is one of the first to investigate the effectiveness of NBS for SMA beyond clinical trial populations.

“The research shows the effectiveness of newborn screening for spinal muscular atrophy in the broader population,” says the lead author of the study Dr Didu (Sandi) Kariyawasam in the School of Clinical Medicine, UNSW Medicine & Health, and a paediatric neurologist at SCHN.

“It’s an important study for building the evidence base that newborn screening is an approach that leads to better health outcomes for children with spinal muscular atrophy and is impactful enough to justify widespread adoption,” says Professor Michelle Farrar in the School of Clinical Medicine, UNSW Medicine & Health, and a paediatric neurologist at SCHN.

SMA is a childhood-onset motor neuron disease. Left untreated, it is a potentially fatal genetic condition caused by a missing or faulty SMN1 gene, which leads to progressive muscle weakness and wasting in babies – limiting their ability to move and sometimes feed and breathe independently.

Clinicians are usually only able to diagnose and treat SMA after symptoms have appeared. By that point, many have already and irreversibly lost up to 90 per cent of their motor nerves, which is why earlier detection is vital.

Until recently, SMA was the leading genetic cause of infant mortality worldwide, with many babies born with type 1 SMA, its severest infantile-onset form, dying before their second birthday.

For the study, researchers followed 15 children diagnosed with SMA using NBS (screening group) and 18 children diagnosed by clinical referral (comparator group) for two years from diagnosis. Children within both groups had the potential to access disease-modifying therapeutics.

The two-year survival rate was 93 per cent in the screening group and 89 per cent in the comparator group. But of the survivors, 11 could walk independently or with assistance in the screening group, compared with just one child diagnosed via a traditional clinical pathway.

SMA screening has now been recommended by the Australian Government to be rolled out nationally with support from the research team, who will help develop standardised guidelines.

The research team are also investigating the viability of other genetic diseases to be incorporated into NBS programs.
“All the work is a multidisciplinary effort between scientists, screening clinicians and allied health, demonstrating that clinical research can make a real positive difference to the lives of children and their families,” Dr Kariyawasam said.