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Newborn Screening for SMA - Can a Wait-and-See Strategy be Responsibly Justified in Patients With Four SMN2 Copies?
Astrid Blaschek1, Heike Kölbel2, Oliver Schwartz3
1Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, Munich, Germany.
Insights
Early treatment is crucial for spinal muscular atrophy (SMA) patients with four SMN2 copies. A proactive approach, initiating treatment before symptoms appear, prevents irreversible disease progression in these infants.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Newborn screening (NBS) for spinal muscular atrophy (SMA) enables early intervention, significantly improving outcomes for infants.
- A consensus on the optimal treatment strategy for SMA patients with four copies of the SMN2 gene remains elusive within the medical community.
Purpose of the Study:
- To establish a responsible treatment strategy for SMA patients identified with four SMN2 copies through newborn screening.
- To evaluate the efficacy of early intervention versus a watchful waiting approach in this specific SMA patient subgroup.
Main Methods:
- Retrospective analysis of 21 SMA patients with four SMN2 copies identified via German NBS projects over three years.
- Inclusion criteria: SMA diagnosis via NBS, age >12 months at last examination, and confirmed four SMN2 copies.
Main Results:
- Fifteen patients underwent long-term follow-up; eight treated presymptomatically (3-36 months) showed no disease symptoms.
- Seven patients on a watchful waiting strategy developed clinical or electrophysiological onset between 1.5-4 years; two did not achieve full recovery despite delayed treatment.
Conclusions:
- A significant proportion of SMA patients with four SMN2 copies develop irreversible symptoms within four years if a 'wait-and-see' approach is adopted.
- These findings support a proactive treatment strategy, advocating for early intervention in SMA patients with four SMN2 copies to prevent disease progression.
Background:
Early treatment after genetic newborn screening (NBS) for SMA significantly improves outcomes in infantile SMA. However, there is no consensus in the SMA treatment community about early treatment initiation in patients with four copies of SMN2.
Objective:
Approach to a responsible treatment strategy for SMA patients with four SMN2 copies detected in newborn screening.
Methods:
Inclusion criteria were a history of SMA diagnosed by NBS, age > 12 months at last examination, and diagnosis of four SMN2 copies at confirmatory diagnosis.
Results:
21 patients with SMA and four SMN2 copies were identified in German screening projects over a three-year period. In three of them, the SMN2 copy number had to be corrected later, and three patients were lost to follow-up. Eight of the fifteen patients who were subject to long-term follow-up underwent presymptomatic therapy between 3 and 36 months of age and had no definite disease symptoms to date. Five of the other seven patients who underwent a strict follow-up strategy, showed clinical or electrophysiological disease onset between 1.5 and 4 years of age. In two of them, complete recovery was not achieved despite immediate initiation of treatment after the onset of the first symptoms.
Conclusion:
A remarkable proportion of patients with four copies of SMN2 develop irreversible symptoms within the first four years of life, if a wait-and-see strategy is followed. These data argue for a proactive approach, i.e., early initiation of treatment in this subgroup of SMA patients.
