Neonatal screening for SMA

Minnesota Newborn Screening: The Addition of SMA

Posted on February 6, 2018

Maggie Dreon, MS, CGC, Sondra Rosendahl, MS, CGC, and Bridget Busacker, MA, Minnesota Department of Health

Minnesota continues to be a leader in the country for timely and well-executed newborn screening. In 2017, Minnesota’s program added three new disorders (X-ALD, MPS I, and Pompe disease) to the newborn screening panel. In 2018, Minnesota will be one of the first states to start screening for spinal muscular atrophy (SMA).

SMA is the leading genetic cause of early childhood death, affecting as many as one in every 6,000 live births. SMA is a neurodegenerative disease, characterized by muscle weakness and atrophy resulting from the deterioration and loss of the lower motor neurons.

SMA is caused by mutations in the SMN1 gene. A second gene, SMN2, often called the “back-up gene,” informs which type a child has. There are four types of SMA based on age of onset and highest motor milestone reached.

While onset of symptoms range from birth to adolescence, the symptoms tend to be nonspecific. Type I is the most common and most severe with death occurring within the first two years of life.

Until recently, families often had little hope given treatments focused on symptom management, rather than symptom mitigation. A year ago, that changed when the drug Spinraza (nusinersen) was approved by the FDA to treat all ages and types of SMA.

Newborn screening seeks to identify children with rare, hidden disorders before the onset of symptoms in order to prevent serious health complications. Given the recent FDA approval of Spinraza, SMA became a relevant disorder for consideration of newborn screening. Over the past year, Minnesota’s Newborn Screening Program worked closely with the CDC to develop and refine a test method for population-wide screening of SMA.

In parallel, Minnesota was equipping the program’s Advisory Committee on Heritable and Congenital Disorders with information about SMA to help them evaluate its candidacy for newborn screening.

In October 2017, Minnesota advisory committee members voted to recommend to the Commissioner of Health the addition of SMA to the newborn screening panel. The addition of SMA was approved in December 2017 and Minnesota will begin screening for SMA early in 2018.

Minnesota’s Newborn Screening Program expects to identify approximately 6-14 newborns with SMA each year.

In Minnesota, SMA screening will target the specific genetic change that is responsible for about 95 percent of cases. This specific change is the loss of exon 7 in both SMN1 genes. Minnesota will not be screening to determine the number of SMN2 genes. This means that children identified to have exon 7 absent will very likely have SMA, though the type will be unknown.

Upon the identification of an abnormal result, the program’s genetic counselors will contact the primary care clinic to discuss the result. They will provide the clinician with the result, a provider fact sheet, a family fact sheet, and a resource list of treatment centers available for consultation. These treatment centers will perform a comprehensive diagnostic evaluation on the child, including the determination of SMA type.

It is important to point out that while the program expects to identify all cases of SMA resulting from the loss of exon 7 in both SMN1 genes, there are about 5 percent of cases caused by different, rarer genetic changes. Minnesota’s current method will not screen newborns for these other changes, and therefore, false negative results are likely.

As with all disorders on the newborn screening panel, if you have clinical suspicion, diagnostic testing should be pursued regardless of a child’s newborn screening result.

http://mnaap.org/newsletter/minnesota-newborn-screening-the-addition-of-sma/