Initial misdiagnosis common for adults with SMA type 2, 3 in Korea
Delay in SMA diagnosis significantly longer for those with type 3: Study
Nearly two-thirds of adults in South Korea with spinal muscle atrophy (SMA) type 2 or type 3 were initially misdiagnosed, according to a recent study.
In type 2 cases, the primary misdiagnosis was a developmental delay, while muscular dystrophy was the main misdiagnosis in type 3 cases. Despite a similar number of clinical visits before a confirmed SMA diagnosis, the wait was significantly longer for people with SMA type 3 than for those with type 2.
The study, “Diagnostic Journey of Korean Patients with Spinal Muscular Atrophy,” was published in the Yonsei Medical Journal.
SMA is a genetic disease caused by mutations in the SMN1 gene. These mutations disrupt the production of SMN, a protein essential for nerve cells that control movement, leading to muscle atrophy (wasting) and weakness. The condition is classified into different types based on the age of symptom onset.
The number of copies of a second SMN2 gene influences disease severity. This gene produces a small amount of SMN protein, which can partially compensate for the loss of SMN caused by SMN1 mutations. A higher number of copies of the SMN2 gene are associated with less severe disease.
Early and accurate diagnosis, treatment essential for best outcomes
Due to the progressive nature of SMA and recent advances in disease-modifying treatments, such as Spinraza (nusinersen), Evrysdi (risdiplam), and Zolgensma (onasemnogene abeparvovec), early and accurate diagnosis and treatment have become increasingly essential.
Still, an early and accurate SMA diagnosis can be challenging, with many factors contributing to a delayed or incorrect diagnosis. These include a lack of disease awareness among medical professionals, variability in disease symptoms, the need for specialists, and limited facilities for genetic testing.
“No study has analyzed the difficulties of the diagnostic process in adults with SMA,” according to researchers at the Yonsei University College of Medicine, in South Korea.
The team reviewed the diagnostic histories of 38 adults with SMA, including 18 men and 20 women. Nine had SMA type 2, and 29 had SMA type 3.
Deletion mutations were detected in all patients, meaning part of their SMN1 gene was missing. Of the 25 patients with available data, all those with SMA type 2 had three copies of the SMN2 gene, eight (42%) of the type 3 patients had three copies, and 11 (58%) had four copies.
At a median age of 3 years, the most common first symptom in type 2 patients was delayed sitting posture, while it was unsteady walking in type 3 patients.
Nearly two-thirds of cases (63%) were initially misdiagnosed, with no significant difference in the proportion of those with type 2 or 3 (56% vs. 66%).
Needle electromyography, which assessed the health of muscles and the nerve cells that control them, was the most common test performed (92%). This was followed by muscle biopsy in 22 patients (58%). About half (53%) underwent genetic testing for muscular dystrophy, which was more commonly performed in type 3 than in type 2 cases (62% vs. 11%).
Median diagnostic delay for patients: 21 years for type 3 and 3 years for type 2
The median age at diagnosis was 25 years, while the median diagnostic delay was 19.6 years and was significantly longer for type 3 than for type 2 patients (median of 21.0 vs. 3.0 years).
Across three time periods examined — 1996-2004, 2005-2013, and 2014-2022 — the age at symptom onset, age at diagnosis, and length of diagnostic delay significantly increased as time progressed. However, the number of clinic visits before diagnosis was similar, regardless of the period.
In addition, no significant difference was observed in the number of prediagnostic clinical visits between type 2 and 3 patients, and these were not significantly associated with the age at symptom onset and diagnosis for all patients.
At diagnosis, all patients showed weakness in the proximal muscles (trunk, shoulders, and thighs). Most (80%) had scoliosis, which is an abnormal sideways curvature of the spine, and about two-thirds (63%) had breathing problems. Mechanical breathing support was used significantly more often in type 2 than in type 3 patients (56% vs. 14%). The two groups had similar creatine kinase blood levels, a muscle damage marker.
“Our investigation represents the first examination of the diagnostic journey in Korean patients with SMA,” the researchers concluded. “As treatments for SMA evolve, the significance of an accurate diagnosis has increased, highlighting the importance of reviewing the diagnostic advancements made thus far.”
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