Early detection of spinal muscular atrophy through newborn screening dramatically improves the effectiveness of all available treatments for this disease.
The European Alliance for Newborn Screening in Spinal Muscular Atrophy demands that by 2025, newborn screening programmes in all European countries include a test for spinal muscular atrophy for all newborn children.
Newborn screening (NBS) is the practice of testing all babies in their first days of life for certain disorders that are treatable, but difficult or impossible to detect clinically. This allows for the identification of patients before the first symptoms emerge.
Newborn screening involves the use of existing methods that can detect spinal muscular atrophy when the child is a few days or weeks old.
It is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt irreversible motor neuron loss and disease progression.
This is especially critical in SMA Type 1, where motor neuron degeneration starts before birth and escalates quickly.
Starting treatment at this time means the child has a chance of a reasonably normal life without developing all disease complications.
Spinal muscular atrophy is a rare disease linked to a biallelic deletion of the SMN1 gene, which leads to an SMN protein deficiency. All SMA patients carry one to six SMN2 genes that influence the severity of the disease. The more SMN2 gene copies a patient has, the milder the disease severity.
In contrast to the SMN1 gene, each SMN2 gene produces only about 10% functional SMN protein. The reduced SMN protein level results in progressive and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement.
The SMA NBS Alliance requests the widespread implementation of newborn screening in babies’ first days of life for the biallelic deletion of the SMN1 gene. This has to be immediately confirmed in addition to determining the number of SMN2 copies.
There is a broad range of patients with SMA. It ranges from neonates suffering from severe problems right at the beginning of their life, up to the onset of the disease later in life with only mild motor disabilities. SMA induces not only motor restrictions, but often severe respiratory disorders, with most needing invasive ventilatory support. Most SMA type 1s and some type 2s require respiratory support and have severe swallowing problems
Over the past three years, treatments for SMA have arrived on the European market. These treatments increase the production of SMN proteins and therefore prevent the death of motor neurons and the progressive loss of function. They do not however save, or repair already affected motor neurons. Neuronal turnover is very low, and therefore what is lost, is lost forever.
New treatments allow children with a severe form of SMA to survive beyond two years of age and retain some motor abilities. It is therefore essential to treat these patients before the onset of the first symptoms.
Ensuring safe and efficient treatment in the days following birth
Various scientific studies around the world showed that treating patients before the onset of the first symptoms could preserve the nervous system and prevent the onset of functional disabilities. Some children detected and treated in the first week of life can benefit from normal functional development.
SMA detection in newborn screening
Spinal muscular atrophy linked to the SMN1 gene is characterised by a biallelic deletion of SMN1 on both chromosomes 5. The detection of a biallelic deletion of SMN1 by newborn screening has to be confirmed by a second independent blood sample and a different test, which also allows the determination of the number of SMN2 copies, essential for the choice of therapy. Caveat: About 3–5% of newborns carrying other SMN1 mutations than the biallelic deletions will be missed by newborn screening.
Ensuring safe and efficient treatment in the days following birth
Various scientific studies around the world showed that treating patients before the onset of the first symptoms could preserve the nervous system and prevent the onset of functional disabilities. Some children detected and treated in the first week of life can benefit from normal functional development.
SMA detection in newborn screening
Spinal muscular atrophy linked to the SMN1 gene is characterised by a biallelic deletion of SMN1 on both chromosomes 5. The detection of a biallelic deletion of SMN1 by newborn screening has to be confirmed by a second independent blood sample and a different test, which also allows the determination of the number of SMN2 copies, essential for the choice of therapy. Caveat: About 3-5% of newborns carrying other SMN1 mutations than the biallelic deletions will be missed by newborn screening.
Techniques to detect spinal muscular atrophy at birth
Several large-scale pilot studies are underway, including in Belgium and Germany. Please see “One Year of Newborn Screening for SMA – Results of a German Pilot Project” and “Newborn Screening for SMA in Southern Belgium” for the initial published results. There is an ongoing pilot in Italy with further European pilots in the planning stages
One technical and organisational solution involves the addition of one single blood spot onto the Guthrie’s testing card to be screened for SMA. This technique is already commonly used for newborn screening panels for various diseases in Europe. So far, no false positives have been detected in pilot studies using this method. These techniques do not allow for accidental findings, as it is only focusing on the SMN1 gene.
Cost
SMA can be added to the current Guthrie test without many additional costs. This cost has to be compared to the psychological and societal impact of the death of babies in the first years of their life, and the lifetime cost of caring for a child with a serious disability.
Ethical considerations
Adding SMA to newborn screening panels intends to identify newborn babies at risk of developing a particularly disabling disease. SMA meets the World Health Organization criteria for being added to newborn screening.
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