Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive degeneration of anterior horn cells from SMN1 deficiency.

• Incidence 1 in 10,000 live births; carrier frequency 1 in 40 to 60.

• SMN2 copy number modifies severity.

• Types: type 0 (prenatal), type 1 (Werdnig-Hoffmann, onset under 6 months, never sits), type 2 (sits, never walks), type 3 (Kugelberg-Welander, walks), type 4 (adult).

• Untreated type 1 mortality is high by 2 years from respiratory failure.

• Hypotonia, symmetrical proximal weakness (legs more than arms), areflexia, tongue fasciculation, bell shaped chest with paradoxical breathing.

• Normal cognition, preserved extraocular and facial movement.

• Scoliosis, contractures, feeding difficulty, recurrent chest infection.

• SMN1 homozygous deletion (95%) by MLPA or quantitative PCR; SMN2 copy number.

• CK normal or mildly raised; EMG shows denervation (not required).

• Newborn screening where available allows presymptomatic treatment.

• Cascade carrier testing and prenatal diagnosis.

Disease modifying therapy, ideally before symptoms

• Nusinersen 12 mg intrathecal on days 0, 14, 28, 63, then every 4 months.

• Onasemnogene abeparvovec (single IV gene therapy, 1.1 x 10^14 vg/kg) for children under 2 years; steroid cover (prednisolone 1 mg/kg), monitor liver enzymes, platelets, troponin.

• Risdiplam oral 0.2 mg/kg daily (up to 5 mg daily over 20 kg).

• Supportive:

• Respiratory care: cough assist, non invasive ventilation, vaccination, early antibiotics.

• Nutrition: gastrostomy, reflux management. Orthopaedic: bracing, spinal fusion for scoliosis, hip surveillance.

• Physiotherapy, wheelchair, vitamin D and bone health.

• Genetic counselling.