Newborn screening improves health outcomes in infants with spinal muscular atrophy
Spinal muscular atrophy (SMA) is a severe genetic disease associated with mutations in the SMN1 gene (SMA5q). The pathological characteristics of SMA involve atrophy of spinal cord motor neurons, leading to weakness and muscle atrophy. The consequent muscle weakness results in most cases in immobility and respiratory failure.1 Clinicians are usually only able to diagnose SMA after symptom onset; however, by this point, many patients may have lost up to 90% of their motor neurons.2 Therefore, early detection is of paramount importance so that treatments can be introduced whilst motor neurons are still viable. The genetic basis of SMA is very homogenous, with 95-98% of cases arising due to a bilateral loss of the SMN1 gene. Therefore, genetic screening for SMA is extremely accurate and can be performed from a dry blood drop-newborn bloodspot screening (NBS).1
Newborn screening is imperative for the early diagnosis of SMA and consequently can lead to access to more effective treatment.2 Although there is currently no cure for SMA, NBS facilitates the early implementation of disease-modifying therapies and can lead to better health outcomes than conventional clinical diagnosis pathways.
A recent study conducted at Sydney Children’s Hospital Network (SCHN) by UNSW Sydney researchers hypothesized that children with SMA are more likely to have a better prognosis when diagnosed through newborn screening compared to conventional diagnosis pathways.
“While the development of genetic therapies has been crucial, having a proactive model for early diagnosis is equally as important as an intervention”, stated Didu Kariyawasam, PhD, from the School of Clinical Medicine, UNSW Medicine & Health, and a pediatric neurologist at SCHN.2
The study was conducted at Sydney Children’s Hospital Network, using a non-randomized cohort of 33 participants. The participants were all under the age of 16 with homozygous exon 7 deletions of SMN1. Participants were non-selectively assigned to either a screening group (diagnosed by newborn screening) from August 1st 2018-August 1st 2020, or to a comparator group (diagnosed by clinical referral) from August 1st 2016- July 31st 2018.3 Disease modifying therapies were provided to participants from both groups. The results demonstrated a two-year survival rate of 93% and 89% in the screening and comparator groups, respectively. Despite the similarity between survival rates, of the survivors 11 could walk independently/with assistance in the screening group, compared to just one participant in the comparator group (X2=16·27; p<0·0001). 3 Furthermore, the requirement for non-intensive ventilation and feeding support was seven times higher in the comparator group.
“The burden of care and the morbidity of SMA was drastically lower in the newborn screening group, which has a huge effect on the quality of life for children and their families”, says Michelle Farrar, PhD, in the School of Clinical Medicine, UNSW Medicine & Health, and a pediatric neurologist at SCHN.2
This study demonstrates the importance of newborn screening for SMA and how when combined with early access to disease-modifying treatments, the functional burden and related comorbidities of SMA can be ameliorated.3 A multitude of recent studies support the findings of this study, further providing evidence for the benefits of newborn screening for SMA diagnosis. The plethora of supporting evidence has led to the formation of a European alliance for neonatal screening tests for newborns for SMA that aims to introduce population screening tests for newborns in all European countries by 2025.1 In the United States, the federal government updated the Recommended Uniform Screening Panel to include Spinal Muscular Atrophy (SMA) in July 2018. As of September 2022, 48 states currently screen for SMA.4 Newborn screening may also be beneficial for other genetic diseases- it is estimated that 5% of newborns may have a rare disease that, if diagnosed shortly after birth, could have effective treatments that may be able to improve the prognosis of the disease.5 For example, newborn screening may be advantageous for Duchenne muscular dystrophy, which is the most common inherited muscular dystrophy in children.6
Written by Maggie Hudson
Reviewed by Marta Palhas
- Jędrzejowska M. Advances in Newborn Screening and Presymptomatic Diagnosis of Spinal Muscular Atrophy. Degener Neurol Neuromuscul Dis. 2020 Dec;10:39-47.
- UNSW Sydney Newsroom. Newborn screening for spinal muscular atrophy improves chances of walking and quality of life: study. Jan 2023. (Last accessed: 30 January 2023)
- Kariyawasam DS, D’Silva AM, Sampaio H et al. Newborn screening for spinal muscular atrophy in Australia: a non-randomised cohort study. Lancet Child Adolesc Health. 2023 Jan;S2352-4642(22)00342-X.
- Cure SMA. Newborn Screening for SMA. (Last accessed: 02 February 2023)
- Marchetti F, Corsello G. Genetics and”democracy”. Ital J Pediatr. 2022 Dec;48(1):202.
- Dangouloff T, Boemer F, Servais L. Newborn screening of neuromuscular diseases. Neuromuscul Disord. 2021 Oct;31(10):1070-1080.