What Does SMA Stand For in Medical Terminology?
SMA stands for Spinal Muscular Atrophy, an autosomal recessive neuromuscular disease caused by mutations or deletions in the survival motor neuron 1 (SMN1) gene, resulting in progressive degeneration of motor neurons in the spinal cord and subsequent muscle weakness. 1, 2
Disease Definition and Pathophysiology
- SMA is characterized by loss of lower motor neurons (anterior horn cells) in the spinal cord and brainstem nuclei, leading to progressive symmetrical muscle weakness and atrophy 3
- The condition arises from homozygous mutations or deletions of the SMN1 gene, causing deficiency in the survival motor neuron (SMN) protein 1
- Approximately 96.4% of SMA patients show homozygous absence of SMN1 exons 7 and 8 or exon 7 only, while 3.6% present compound heterozygosity 4
Epidemiology
- SMA affects approximately 1 in 6,000 to 1 in 10,000 live births and is the most common genetic cause of childhood mortality 3, 5
- The carrier frequency is estimated at 1 in 40 to 1 in 60 individuals 5
- SMA is one of the most frequent autosomal recessive diseases with a carrier frequency of 1 in 50 4
Clinical Classification
- Phenotype is classified into four grades of severity (SMA I, II, III, IV) based on age of onset and motor function achieved 5
- Type I SMA has high mortality within the first year of life if untreated 1
- Disease severity correlates inversely with the number of SMN2 gene copies present, though SMN2 cannot completely compensate for SMN1 loss 2, 4
Current Treatment Landscape
- Three FDA-approved therapies exist: nusinersen (Spinraza, an antisense oligonucleotide), risdiplam (Evrysdi, a small molecule), and onasemnogene abeparvovec (Zolgensma, a gene replacement therapy) 6, 2
- Zolgensma works by replacing the malfunctioning SMN gene with a functional variant, providing a one-time treatment that halts disease progression 6
- No single therapy can cure SMA; combination therapies may be essential for comprehensive treatment as SMA affects multiple organ systems 1
Important Clinical Considerations
- Nutritional complications are common, with up to 65% of SMA patients experiencing malnutrition and 84% having calcium absorption issues 7
- Direct molecular genetic testing is easy and rapid, achieving up to 95% sensitivity and nearly 100% specificity 5
- SMA was added to the recommended uniform newborn screening panel in July 2018 in the United States 3