Rapid test allows doctors to start SMA treatment in 9-day-old baby
In-house genetic testing yields results within hours
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- A rapid, in-house genetic test allowed doctors to diagnose SMA in a newborn experiencing poor feeding and weight loss.
- The digital PCR test confirmed the SMA diagnosis within hours, bypassing standard laboratory delays.
- Early detection enabled the baby to begin disease-modifying treatment at 9 days old.
A rapid, in-house genetic test allowed doctors in Japan to confirm a newborn’s diagnosis of spinal muscular atrophy (SMA) within hours and start treatment when the boy was 9 days old.
The baby was readmitted to the hospital eight days after birth because of poor feeding and weight loss. That evening, his newborn screening (NBS) result came back positive for SMA, prompting his referral to the doctors’ hospital for confirmatory testing.
Using a rapid genetic testing method called digital PCR (dPCR), doctors confirmed the diagnosis within 11 hours after receiving the baby’s blood sample, allowing treatment with Evrysdi (risdiplam) to start the next morning.
“This case suggests that a rapid in-house dPCR workflow can shorten the time from a positive NBS result to definitive diagnosis and may facilitate treatment within the early therapeutic window,” researchers wrote in a case report.
The study, “Ultra-early treatment initiated at 9 days of age for spinal muscular atrophy: a case report,” was published in Brain and Development Case Reports.
Early treatment is important
SMA is caused mainly by mutations in the SMN1 gene, most commonly the loss of a key section, exon 7, from both copies of the gene. This leads to a shortage of survival motor neuron (SMN) protein, which motor neurons (the nerve cells that control movement) need to survive. Without sufficient SMN, these cells progressively die, leading to SMA symptoms such as muscle weakness and wasting.
Available SMA treatments can slow or prevent disease progression, but they cannot restore lost motor neurons. Starting treatment as early as possible, ideally before symptoms appear, offers the best opportunity to preserve motor function. For babies expected to develop more severe SMA, evidence suggests that starting treatment within the first two weeks of life may be particularly beneficial.
NBS can identify babies who may have SMA before clear symptoms appear, but a positive result requires genetic testing to confirm an SMA diagnosis. The test also determines the number of copies of SMN2, a backup gene that can produce a small amount of functional SMN. Generally, fewer SMN2 copies are associated with more severe SMA.
In Japan, confirmatory genetic testing is often performed at outside laboratories and can take about five days. Because newborn screening results typically become available about a week after birth, this can make it difficult to start treatment within the first two weeks of life.
To speed the confirmatory diagnostic process, a team of doctors in Japan developed an in-house test using dPCR that can quickly detect the loss of SMN1 exon 7 and determine the number of SMN2 copies.
The rapid test that allowed the boy to start treatment at 9 days of age “would not have been feasible” if confirmatory testing had been sent to an outside laboratory, the researchers wrote.
The baby, born after a full-term pregnancy, had no family history of SMA. After being discharged at 5 days old, however, he developed poor feeding and weight loss and had to go back to the hospital at 8 days.
That evening, his NBS result came back positive for SMA, prompting his referral to the doctors’ hospital. They noticed the baby could move his arms and legs against gravity while crying, although his limbs tended to remain extended at rest. He did not show other characteristic signs of SMA, such as abnormal breathing movements or tongue twitching.
His blood sample reached the laboratory at 6:30 p.m. on day 8. Testing began at midnight, and by 5 a.m. the next day, doctors had the result: The baby was missing exon 7 from both copies of SMN1, confirming the SMA diagnosis. He also had three copies of SMN2, which are generally associated with SMA type 2 or 3.
Because the dPCR test was accredited for clinical diagnostic use, no further confirmatory testing was needed. At 10 a.m. on day 9, five hours after the result became available, the baby received his first dose of Evrysdi. After starting Evrysdi, his feeding improved, and he began gaining weight. His parents also noticed stronger vocalizations and more vigorous movements.
His motor abilities, assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), also improved. His score increased from 53 on day 9 to 56 on day 25, shortly before the baby received the one-time gene therapy Zolgensma (onasemnogene abeparvovec-xioi).
While “NBS programs are powerful tools for early detection of SMA, translating a positive result into immediate therapeutic intervention often remains a clinical challenge due to the time required for a conventional confirmatory test,” the researchers wrote, noting that “in ultra-early therapeutic intervention for SMA, every day counts to prevent irreversible motor neuron degeneration.”
“By utilizing a rapid in-house diagnostic system, we can bridge this gap and enable seamless coordination from the definitive diagnosis of SMA through treatment,” the team concluded.
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