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Spinal Muscular Atrophy (SMA)
Newborn in Kerala being treated for spinal muscular atrophy before symptoms set in
Context: In a first-of-its-kind development in India, a newborn diagnosed prenatally with the SMN1 gene mutation (linked to Spinal Muscular Atrophy, SMA) has begun presymptomatic treatment at SAT Hospital in Kerala. The treatment involves Risdiplam, a disease-modifying drug, administered before the onset of symptoms.
What is Spinal Muscular Atrophy (SMA)?
- SMA is a group of hereditary diseases affecting motor neurons.
- Motor neurons are specialised nerve cells in the brain and spinal cord that control muscle movement (arms, legs, face, chest, throat, tongue) and skeletal muscle activity (speaking, walking, swallowing, breathing).
- SMA causes skeletal muscle weakness, often more severe in the trunk (chest) and upper legs/arms than in hands and feet.
- Common complications include: Respiratory infections, Scoliosis (curvature of the spine), Joint contractures (chronic shortening of muscles/tendons).
How Is SMA Classified?
- Based on age of symptom onset and severity:
- Type 0: Severe symptoms before birth; difficulty breathing and feeding at birth (very rare).
- Type I (Werdnig-Hoffman disease): Symptoms before 6 months; severe muscle weakness and breathing/swallowing difficulties.
- Type II: Onset between 6-18 months; can sit unaided but cannot stand/walk independently.
- Type III (Kugelberg-Welander disease): Onset after 18 months; able to walk but with difficulty.
- Type IV: Adult-onset (after 18 years); mild to moderate leg weakness.
What Causes SMA?
- The most common form is caused by mutations in the SMN1 gene (Survival Motor Neuron gene 1).
- There is a similar gene, SMN2, which produces less SMN protein. More copies of SMN2 generally mean milder symptoms.
- SMA leads to insufficient SMN protein, essential for motor neuron health, resulting in neuron loss and muscle wasting.
- Other, rarer forms are linked to mutations in genes like IGHMBP2, MORC2, UBA1, DYNC1H1, BICD2, and TRPV4.
Who is at Risk?
- Autosomal recessive inheritance: Must inherit two faulty SMN1 genes (one from each parent).
- Carriers (with one mutated gene): No symptoms, but can pass the gene.
- Rarely, sporadic mutations can cause SMA without family history.
- Carrier testing is available and recommended if there’s a family history.
How is SMA diagnosed and treated?
- Clinical evaluation: Medical and family history, physical and neurological exams.
- Genetic testing: Detects SMN1 gene deletion or mutation (identifies ~95% of SMA cases).
- Additional tests if needed:
- Electromyography (EMG)
- Nerve conduction studies
- Muscle biopsy (for differential diagnosis)
- While there is currently no cure for SMA, several FDA-approved treatments have significantly improved outcomes:
- Nusinersen (Spinraza): An injectable drug that boosts SMN protein production.
- Onasemnogene abeparvovec-xioi (Zolgensma): A one-time gene therapy replacing the faulty SMN1 gene.
- Risdiplam (Evrysdi): An oral medication that increases SMN protein levels.
