By Michelle Hoard, MS, LCGC; Genomic Science Specialist, Genomic Services & Khalida Liaquat MS, LCGC; Genomic Science specialist, Genomic Services

August 27, 2019 Better Health

Did you know that August is SMA Awareness Month?  Spinal Muscular Atrophy, or SMA, is a genetic disease that affects about 1 in 11,000 babies born each year, regardless of sex or ethnicity1. Approximately 1 in 54 Americans is a carrier of a genetic change that may lead to having a child with SMA if their partner is also a carrier1. These genetic changes in affected individuals lead to damaged motor nerve cells in the spinal cord which eventually deteriorate, impairing movement and physical strength, and ultimately impacting the ability to move, walk, eat, and breathe. SMA is often thought of as a childhood disease. However, symptoms may present at different times throughout life, from gestation through infancy and into adulthood. The younger the age of onset, the more severe the disease and prognosis. This is reflected in the division of the four subtypes of the disease, from SMA type I (most severe) to type IV (least severe). Early diagnosis is critical to allow for access to treatments that have been shown to improve survival and help achieve motor milestones.

Until recently, treatment for this most deadly genetic cause of infant death was only supportive. There are now two groundbreaking therapies that have brought to fruition decades of research and the promise of gene therapy. Both therapies affect the same change: an increased expression of the genes associated with SMA, known as SMN1 and SMN2.

Genetic changes that lead to the loss of SMN1 function are known to cause the disease, yet humans have an almost identical spare copy of the gene (SMN2) that functions effectively only about 15% of the time2.  One therapy which is injected into the cerebrospinal fluid at regular intervals throughout life, aims to increase the efficacy and expression of SMN2 to compensate for the loss of SMN1 production caused by the genetic change. The second therapy, on the other hand, is a gene therapy that was approved as a one-time intravenous dose which aims to deliver a functional copy of the SMN1 gene directly to the motor neurons. In clinical trials for both therapies, an earlier intervention led to better outcomes, which makes the identification of SMA genetic changes critical to medical management and referral to SMA care centers3.

Saving time, saving neurons.  Genetic testing for SMA benefits from a number of different laboratory methodologies today. These advances have led to the ability to detect SMA during the prenatal period through carrier screening, which identifies at-risk couples and gives them the option of fetal diagnostic testing through amniocentesis or chronic villi sampling. In addition, many states have implemented permanent statewide SMA newborn screening programs. Both prenatal testing and rapid postnatal genetic testing after early detection allow for early intervention through treatment. Cure SMA advocates for the SMA community and raises funds to support research into the disease and its treatment.   Because of this advocacy group, a disease once known only by geneticists is now commonly screened for both in couples considering pregnancy and in newborns.

To learn more about Spinal Muscular Atrophy go to:
https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy
http://www.curesma.org

For information about testing for SMA, go to:
https://testdirectory.questdiagnostics.com/test/test-detail/16869/sma-diagnostic-test?p=r&q=SMA&cc=MASTER
or call 1.866.GENE.INFO (1.866.436.3463)

This information is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient. The treating healthcare provider should refer to the manufacturer’s approved labeling for prescribing, warnings, side effects, and other important information.

References

  1. Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens. Eur J Hum Genet. 2012;20:27-32.
  2. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy‐determining gene. Cell 1995;80:155–165
  3. Farrar MA, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2017;81:355-368.