Commentary
Video
Key Updates in SMA Diagnosis: What Clinicians Should Know
Author(s):
In this episode, our panel of experts delves into the latest updates on spinal muscular atrophy diagnosis, focusing on the critical role of newborn screening, early intervention, and evolving classification methods for improved patient outcomes.
Spinal muscular atrophy (SMA) linked to chromosome 5q is an autosomal recessive disorder caused primarily by biallelic variants in the survival motor neuron 1 (SMN1) gene affecting approximately 1 in 15,000 live births. The first publication on SMA standards of care was developed in 2007 and later updated in 2018 by convening an International Conference of SMA experts. Through that, 2 publications were produced and globally distributed.
Years later, the field has significantly changed, with 3 new SMN-enhancing treatments—nusinersen (Spinraza®, Biogen), onasemnogene abeparvovec-xioi (Zolgensma®, Novartis), and risdiplam (Evrysdi®, Genentech)—at clinicians’ disposal. Ultimately, the approval of nusinersen and successful SMA newborn screening pilot programs helped facilitate implementation of SMA newborn screening, which resulted in dramatic change in SMA natural history.
The availability of disease-modifying therapies for 5q SMA and implementation of SMA newborn screening led the urgency to update the SMA best practice recommendations for diagnosis, which were published a few short months ago. These recommendations, led by an SMA working group of American and European health care providers, stress that SMA newborn screening is essential to towards getting an accurate diagnosis for patients. In the paper, the group provided recommendations for characterizing newborn screening-identified infants before treatment; minimum recommendations for starting or offering SMA newborn in a state or country; recommendations for activities and services to be provided by an SMA specialty care center accepting SMA newborn screening referrals; and recommendations for partnership with individuals with SMA and caregivers to support newborn screening-identified infants and their caregivers.
To better understand how these updates may impact SMA diagnosis and clinical care, NeurologyLive® convened a panel of experts who served as study authors on the recommendations. These included Mary Schroth, MD, FAAN, chief medical officer at Cure SMA and a pediatric pulmonologist; Kapil Arya, MD, a pediatric neurologist from Little Rock, Arkansas; Juan Francisco Vazquez Costa, MD, PhD, an adult neurologist who treats motor neuron diseases in Valencia, Spain.
In this first episode, the panel highlighted some of the main points of the recommendations, including the critical importance of early diagnosis and treatment for infants identified through newborn screening. Throughout the discussion the experts emphasized the need for a structured process to notify caregivers and coordinate immediate follow-up with specialized teams to initiate disease-modifying therapies. In addition, they stressed that measurable markers, such as elevated neurofilament levels, show rapid motor neuron loss in infants, reinforcing the urgency of early intervention. Furthermore, the panel discussed the limitations of the traditional SMA classification system.
Transcript edited for clarity.
Kapil Arya, MD: If I can, since I'm a pediatric neurologist and have been involved with newborn screening, especially in the state of Arkansas to a good extent, let me talk about the specific recommendations regarding SMA infants identified by newborn screening. One of our recommendations is that there should be a clear process for notifying infant caregivers, as well as coordinating initial visits after SMA newborn screening. Most states have personnel who are updated with newborn screening results, but the parents need to be informed properly. They should understand the importance of very close and early follow-up with a specialist, so treatment can be considered and initiated urgently. There definitely needs to be a process for referring these infants with SMA to the appropriate specialists.
At those specialized centers, a collaborative team that includes experts should evaluate the child’s motor function. That specialist team should also be well aware of potential pitfalls, such as approval for disease-modifying therapies, and determine the most efficient process for coverage, cost, and reimbursement. Following this, there should be a well-thought-out system for evaluation and follow-up, which includes education and resources for caregivers. So, in brief, that’s what our team has recommended as the minimum required for SMA infants diagnosed by newborn screening.
Mary Schroth, MD: I’d like to add to that. It’s essential to have collaboration between the newborn screening laboratory, the primary care provider, and the SMA specialty care team. That communication is crucial. SMA needs to be diagnosed and treated as quickly as possible. What my neurology colleagues always say is that "time is neurons" when it comes to SMA. The sooner you treat, the better the outcomes.
Kapil Arya, MD: That is quite correct. I completely echo Mary’s point—we are losing thousands of neurons each day. Even a few days' delay in diagnosis and treatment can drastically affect the child’s ability to reach motor milestones. It can also result in additional comorbidities like swallowing or breathing problems.
Juan Francisco Vazquez Costa, MD, PhD: Yes, those are very important points, and they are not just theoretical. These things are measurable with neurofilament levels. We know that before children show symptoms, their neurofilament levels in serum and CSF are very high. This is the best evidence that patients are losing motor neurons rapidly during the first two or three months of life.
Mary Schroth, MD: Another recommendation is that with the availability of truly disease-modifying treatments for SMA, the classification by type no longer applies to everyone with SMA. Historically, we classified by type based on the age of symptom onset and the highest motor development level ever achieved. This still applies to older children and adults. But when it comes to infants treated before or shortly after symptom onset, the type doesn’t really describe their prognosis or clinical status.
The paper we’re referencing agreed that infants should be categorized based on SMN2 copy number, current motor function, age of symptom onset, and the severity of symptoms (if present). While this wasn’t specifically discussed in the paper, after an infant receives treatment, identifying their age at treatment initiation and their motor function at the time of treatment is important as well. We’re still learning about the impact of these treatments on disease progression, but categorizing infants in this way will help us better understand outcomes.
