Medically reviewed by Susan Kerrigan, MD and Marianne Madsen
We live in a time where early detection for numerous diseases and conditions is not only possible but can make all the difference in determining the right care and treatment–and receiving it in the most expedient way. One of the most critical times in life for screening for diseases begins at birth.
A pilot program in Australia is looking at the importance of testing for spinal muscular atrophy (SMA) in newborns, while identifying patients across socioeconomic and cultural demographics, in order to mitigate inequity and provide patients with access to multidisciplinary treatment.
Early diagnosis and treatment initiation is key for patients with spinal muscular atrophy (SMA), an inherited degenerative neuromuscular disease characterized by muscle weakening, atrophy, and death in infants. A recent study published in Developmental Medicine & Child Neurology found that a pilot newborn screening program in Australia identified at-risk patients with high specificity and could be effectively incorporated into clinical practice.
What is spinal muscular atrophy?
Spinal muscular atrophy (SMA) is an inherited (genetic) condition that affects the nerve cells that carry messages from the brain to the muscles of the body. The brain uses nerves called motor neurons to control muscle movement. Motor neurons need the survival motor neuron (SMN) protein to work correctly.
In SMA, a baby’s body cannot make enough SMN protein. When a baby cannot make enough SMN protein, motor neurons die, damaging the connection between the brain and the muscles. The brain will then have trouble telling the muscles to move, which causes the muscles to break down.
This results in muscle weakness and decreased muscle size (atrophy), which can cause breathing and swallowing difficulties. Loss of motor neurons also leads to other signs and symptoms of the condition.
There are several forms of SMA, and the severity of the condition depends on how much normal SMN protein a baby makes.
The study authors stated that newborn bloodspot screening (NBS) in Australia “continues to be one of the most successful population health programs, yielding greatly improved health outcomes for identified cases achieved by a combination of very early diagnosis and expedient initiation of treatment and management.” They suggested adding SMA to newborn screening panels could enhance the quality, efficiency, and efficacy of NBS programs based on the pilot study results.
The New South Wales and the Australian Capital Territory NBS program, in which parents are urged but not required to enroll their newborns, offers screening for over 30 congenital conditions and typically screens approximately 100,000 newborns each year. For SMA, the absence of SMN1 exon 7 alleles was considered screen positive. The authors noted that this does not detect heterozygous deletions or point mutations on the SMN1 gene, which account for about 2%-5% of the SMA population. SMN2 copy number did not factor into screen positivity, to allow for proficiency testing in the pilot study.
A total of 252,081 newborns were screened in the NBS program over the study period (August 2018 to January 2021), and 22 had positive screenings for SMA. Of those infants, 21 had confirmed SMA with homozygous deletions in exon 7 of SMN1. Twelve of these infants had 2 copies of SMN2, 8 had 3 copies, and 1 infant had 4 copies. Greater SMN2 copy number generally correlates with milder phenotypes.
Participants received positive screening results a median of 3 days after birth, received diagnostic confirmation a median of 15 days after birth, and therapy initiation at a median of 25 days after birth. The overall incidence of SMA in the program during the study period was 1 in 11,458 newborns. Compound muscle action potentials (CMAPs) were recorded at diagnosis, and there were significant differences between infants with different SMA genotypes. One of 3 newborns included in longitudinal assessment of CMAPs showed significant reductions in amplitude at symptom onset. Overall, these findings suggest NBS is crucial for diagnosis prior to motor neuron degeneration.
More than 99.9% of all newborns in New South Wales were included in NBS, which had a sensitivity rate of 100%, specificity greater than 99.9%. The false-positive rate was less than 0.001%, and the positive predictive value was 95.5%.
Implementation challenges included shipping delays, which lengthened time to completing the diagnostic workups, including SMN2 copy number results. This was addressed by the NBS laboratory obtaining accreditation for SMN2 testing with digital droplet polymerase chain reaction on dried blood spots. Another challenge was managing urgent referrals. NBS staff partnered with neuromuscular specialists to work the NBS SMA pilot into established pathways and neuromuscular models of care.
Multidisciplinary collaboration and communication between a neuromuscular team, families, and community health care providers also proved important. Study authors noted that a decision support analysis and national clinical guidelines for SMA are warranted.
Treatment and management
Two new treatments can change how the genes work in some cases of SMA. A medicine called nusinersen can help the SMN2 gene make more SMN protein. Gene therapy can replace the nonworking SMN1 gene with a working copy. It is important to talk to your healthcare provider about which treatment(s) are best for your baby. The goal of these treatments is to prevent muscle weakness and resulting health problems.
Some children with SMA will require other types of support that can include:
- Physical therapy
- Feeding support for babies who cannot swallow
- Breathing support
The outcomes of these treatments vary depending on the form and severity of the condition.
Overall, the results of the pilot program suggest SMA testing within NBS provided opportunities for early intervention in newborn patients and gave all families — regardless of financial, geographic, cultural, or linguistic barriers — access to appropriate diagnosis and care for SMA.
“The results from this study can be used as a blueprint for NBS programs globally, as they work to expand the number of disorders screened, alongside providing a personalized model of care for identified individuals,” the authors concluded.
