Enhancing SMA Care Through Early Diagnosis and Family Education

Spinal muscular atrophy (SMA) is a complex, progressive neuromuscular disorder that requires a multidisciplinary approach to care. The central role of neurology clinics in coordinating SMA care, the importance of shared decision-making with families, and best practices for educating caregivers on the disease’s nature and treatment options are key topics discussed by John Brandsema, MD, a pediatric neurologist at Children's Hospital of Philadelphia, in this Q&A with The American Journal of Managed Care^® (AJMC^®).

In part 1 of this discussion, Brandsema highlighted the transformative impact of newborn screening in enabling early diagnosis and intervention, while also stressing the need for vigilance in identifying cases that may not be detected through standard screening.

John Brandsema, MD

AJMC: What is your role in the management of patients living with SMA?

Brandsema: Most times, the neurology clinic is the medical home for people with SMA, and we try our best to have all of the different perspectives that they might need for their care in one place. We try to be the nexus for referrals to a network of providers and other aspects of care delivery that the patient might need in some areas of the country. It may be a physical medicine and rehabilitation specialist that runs the neuromuscular clinic. And I've even seen some contexts where it was a pulmonologist or an orthopedic surgeon or somebody involved in the SMA care team. But the key for people living with SMA is to be linked with a center where there are multiple specialists that have insight into the care for this rare disease.

AJMC: How do clinicians work with patients with SMA and their families to set realistic treatment goals and expectations?

Brandsema: It's always a collaboration. We're trying our best to understand the medical situation that the person is in with their disease, but also what is important socially and culturally to the family in their decision-making and being respectful of that in coming to a mutual place where we can agree upon what might be the best course of action for the person living with SMA to choose. It can be sometimes complex, especially now in the era of having multiple treatment options available for SMA and also the changing landscape of the standard of care. In the context of being on disease-modulating therapy, we need to continue to be open-minded and thorough in having our discussions so that we can understand best how to move forward together.

AJMC: What are the best practices for educating families and caregivers on SMA and its debilitating nature?

Brandsema: It depends a lot on when you're meeting the family relative to the person's experience of SMA. We get prenatal referrals sometimes where the parents have tested positive as carriers and choose to have their fetus tested and know that the baby will be affected with SMA. We have families that are introduced to us in the newborn period after a positive newborn screening diagnosis. Then, we have those who come symptomatic with weakness and receive their diagnosis that way, and it's a different conversation in those contexts in terms of both understanding the landscape of what tends to happen in natural history and how we might be able to intervene with disease-modulating treatments. The key to understanding any neurodegenerative disease is that they are relentlessly progressive. In natural history, we have an understanding of what to expect relative to somebody's SMN2 copy number and other factors that may play into their clinical presentation if they're symptomatic.

But in the role of a pre-symptomatic diagnosis, whether it be a fetal referral or in newborn screening where the baby does not have any detectable symptoms, the conversation is starting to be very different because we often can offer disease-modulating therapy before any symptoms are evident, which makes for a very different experience of the disease. It's obviously very difficult for families to hear that a loved one is facing a disease that's neurodegenerative, but there is hope in today's world with disease-modulating therapy that the disease is modifiable, and yet we have no cure for this disease.

We need to understand that somebody diagnosed with SMA will be living with that deficiency of the SMN protein for life and may have symptoms develop at any time relative to that. Therefore, being connected with an SMA care team to ensure that they have the best possible optimization of their health status and their standard of care is very important.

AJMC: In your opinion, what are the best clinical practices to ensure a timely diagnosis of SMA?

Brandsema: It's been encouraging and remarkable to see the speed with which newborn screening was adopted across the US relative to this rare disease, compared with the pace of some earlier diseases.

Being able to have a diagnosis of about 95% of our affected individuals with SMA through newborn screening has led to early identification, early treatment, and a very different landscape of who we might expect to meet affected by SMA.

Of course there is an exception to the newborn screening approach: people who don't have a homozygous deletion of their SMN1 genes as the reason why they have SMA but rather have a point mutation or some other genetic mutation that's causing at least 1 of their SMN1 copies to be nonfunctional. Those people will be missed by newborn screening and will still come in symptomatic, along with those in areas where newborn screening may not have been available for somebody until very recently.

Because of those rare 5% of individuals who are still going to present symptomatically, it's very important for frontline providers to still be aware of this disease and what its earliest signs and symptoms are, because early diagnosis is so critical. Once we lose a motor neuron, it's not able to be regenerated in any way with current treatment and science. This is an irreversible loss of something very important that happens in this disease.

We, therefore, need to ensure that any person who presents with symptoms of motor delays in childhood or progressive weakness—especially if there's bulbar involvement, which means swallowing and breathing impairment—is screened for this disease through having appropriate genetic testing to ensure that there is a timely diagnosis. In older individuals who might have milder forms of this disease that are more slowly progressive, there is a diagnostic odyssey for a lot of patients that can take years before they receive a diagnosis, and during that entire time, their motor neurons may become lost without treatment. It's really critical to have vigilance and early testing. There are sponsored testing protocols now that allow for genetic testing without any financial obligation from the patient, and you need to remember that even if you've had a newborn screen done, you've only looked for 95% of the people with SMA. That other 5% still need full sequencing of their SMN1 gene to be sure.