A new case report highlights the difficulties in detecting spinal muscular atrophy (SMA) when it presents mildly.
Symptoms of muscular atrophy in the spine (SMA) often appear early and with significant mobility impairment, but patients with milder phenotypes can often present a diagnostic challenge.
In a new case report published in Journal of Neurological Sciences, the authors recalled one such case involving a 32-year-old woman whose initial symptoms were relatively minor: mild weakness in the waist and increased fatigue when climbing stairs.
“While the severe presentation is much clearer in childhood, the milder phenotype seen in adulthood (SMA type III or IV) can be misleading for adult neurologists and radiologists who are generally less familiar with the disorder. ”, they said.
The patient in the case report had a negative family history for neuromuscular conditions, and aside from her muscle weakness, her only other notable health condition was hypothyroidism, the authors explained. At 31 years of age, the patient underwent a neurological examination, which revealed mild symmetrical proximal weakness in both extremities and lack of deep tendon reflexes in the lower extremities. She also had elevated serum creatine kinase activity. Other evaluations, such as cranial nerve and sensory exams, were normal, the authors said.
The patient’s pelvic girdle and thigh muscles were examined by magnetic resonance imaging. The scan showed diffuse and severe fatty transformation and atrophy in MOST muscle groups, initially leading investigators to believe his problems were myopathic. However, when THEY performed an electromyography (EMG), they found chronic neurogenic changes in every muscle they investigated, as well as “occasional” fasciculations. The authors said this was a crucial diagnostic clue pointing toward a neurogenic cause.
They decided to do genetic testing and headed SMN1 Genetic analysis confirmed a diagnosis of 5q SMA (so named because deletions are present in the long arm [q] of chromosome 5). The patient was eligible for gene therapy, but she chose not to do so due to the mild course of her disease and the desire to become pregnant.
The researchers said the case highlights a number of diagnostic “pitfalls” in milder cases of SMA, such as the risk of mistakenly assuming muscle weakness is myopathic in nature.
Another potential problem, they said, can arise in the genetic testing phase. In this case, exome sequencing was initially negative, and SMA was only confirmed once researchers performed SMA-specific tests. SMN1 gene.
The authors said that it is common to use next-generation sequencing (NGS) to look for possible neuromuscular disorders, since those disorders can be genetically heterogeneous. However, they added that NGS often misses 5q SMA “due to extremely high sequence homology between SMN1 and its paralogue SMN2.
“Therefore, it is necessary to apply more specific methods, such as multiplex ligation-dependent probe amplification or qualitative polymerase chain reaction,” they said.
For this reason, the study authors said that conventional tools, such as EMG, might still be needed before moving on to genetic testing. They said a muscle biopsy might also have been valuable had diagnostic uncertainty remained.
In their conclusion, the researchers said the case highlights the challenges of diagnosing milder cases of SMA in adults and other patients.
“Most notably, it further emphasizes the need to consider SMA among the differential diagnoses in outpatients with a shoulder girdle pattern of weakness and elevated levels of CK activity, especially in view of potential therapeutic consequences in the age of gene-based therapies. they wrote.
Reference
Krenn M, Jengojan S, Grisold W. Spinal muscular atrophy presenting with mild limb girdle weakness in adulthood: diagnostic pitfalls in the era of disease-modifying therapies. J Neurol Sci. Published online July 25, 2022. doi:10.1016/j.jns.2022.120347