Arun S. Varadhachary, MD, PhD provides an overview of the case of a 28-year-old male with spinal muscular atrophy, describes the 4 main phenotypes of SMA, and considers how average age of onset impacts patient prognosis.
Arun S. Varadhachary, MD, PhD: This is a case of a 28-year-old young man who received a diagnosis of with SMA [spinal muscular atrophy] at the age of 16. Initially, he sought help with physical therapy to help improve function, but he didn't perceive any major improvements and was lost to follow up. When he sought medical care, we received an updated social history. He works as a computer programmer, and he enjoys playing video games in his spare time. Recently, he's noticed that he's developed more weakness in his hands, which is interfering both with his work responsibilities and his recreational activities. He went to his primary care physician, who recognized his past medical history of SMA [and advised that he] engage the input of a neurologist. The neurologist noticed that there was weakness in the hands and muscle groups, particularly in the hips and thighs, which represented progression of the patient's long-standing SMA. The neurologist then educated the patient about what had transpired over the past number of years in the treatment of SMA and began to understand the patient's personal goals for physical function and starting his own family. As a consequence of that discussion, the patient decided to begin treatment for SMA with some exciting available therapies and to reengage with physical therapy and occupational therapy to try to improve his overall level of function. After a discussion with the neurologist, the patient decided to begin treatment with Nusinersen, a drug approved in 2016 to treat SMA. This type of a presentation is actually pretty common. Frequently, patients are given a diagnosis SMA at a point during their youth but believe that they can compensate well enough or that there isn't any direct benefit in interacting with the medical system.
Suddenly, they are lost to follow up. However, they return to medical attention some years later when they’ve had enough erosion in their symptoms and wish to pursue available treatment or anything to help them maintain their level of function. Historically, SMA has been grouped into 4 main types. Although the genetic underpinnings of the disease are the same, the phenotype is based upon the patient’s age at symptom onset. The most severe is type 1 SMA [infantile-onset or Werdnig-Hoffmann disease], which presents at infancy and is very frequently diagnosed at birth in a very weak infant who fails to feed properly or cry. The other types of SMA are designated based upon the highest motor milestones that the individual can reach. Thus, in contrast to type 1 SMA, in which the individual never achieves the ability to sit independently, type 2 SMA [Dubowitz disease] tends to come to medical attention after the infant reaches that first milestone of sitting independently after 6 months of age. Type 3 SMA [juvenile-onset or Kugelberg-Welander disease] is defined by the ability of the individual to reach the walking milestone; medical attention is sought when the child has difficulties walking or begins to lose the ability to walk. That initial presentation doesn't necessarily occur right at the typical time of independent walking (age, 12-18 months) but can occur during the toddler through teenaged years. Type 4 SMA is defined as symptoms that begin after 20 years of age. This type is relatively rare, and the frequency of this particular presentation remains unclear. From the epidemiologic standpoint, the incidence is probably highest for type1 SMA. However, because of the severity of its prognosis and the many individuals who die before 2 years of age, the prevalence of SMA tends to cluster around patients with type 2 and 3 disease.
Transcript Edited for Clarity