SMA is characterized by muscle weakness and atrophy resulting from progressive degeneration and irreversible loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. The onset of weakness ranges from before birth to adulthood. The weakness is symmetric, proximal greater than distal, and progressive. Poor weight gain with growth failure, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties are common complications of SMA.
Bulbar dysfunction is universal in individuals with SMA I; the bulbar dysfunction eventually becomes a serious problem for persons with SMA II and only very late in the course of disease for those with SMA III. Gastrointestinal issues may include constipation, delayed gastric emptying, and potentially life – threatening gastroesophageal reflux with aspiration. Growth failure occurs due to gastrointestinal issues in SMA I patients. Non-ambulatory individuals with SMA II and III are at risk of developing obesity.
Children with SMA I and II (and more rarely, type III) have progressive decline in pulmonary function due to a combination of weak respiratory muscles, reduced chest wall and lung compliance, and a reduction in alveolar multiplication. Respiratory failure is the most common cause of death in SMA I and II. Decreased respiratory function leads to impaired cough with inadequate clearance of lower airway secretions, hypoventilation during sleep, and recurrent pneumonia.
Scoliosis, hip dislocation, and joint contractures are common complications in individuals with SMA. Scoliosis is a major problem in most persons with SMA II and in half of those with SMA III. Approximately 50% of affected children (especially those who are non – ambulatory) develop spinal curvatures of more than 50 degrees (which require surgery) before age ten years. Later in the disease course, non – ambulatory individuals can develop thoracic kyphosis.
An unexplained potential complication of SMA is severe metabolic acidosis with dicarboxylicaciduria and low serum carnitine concentrations during periods of intercurrent illness or prolonged fasting.Whether these metabolic abnormalities are primary or secondary to the underlying defect in SMA is unknown. Prolonged fasting should be avoided to prevent this complication. Pre-symptomatic individuals should be monitored for the development of symptoms to determine appropriate timing to initiate targeted and/or supportive therapies. Individuals with SMA are evaluated at least every six months; weaker children are evaluated more frequently.
Multidisciplinary surveillance at each visit includes assessments of nutritional state, respiratory function, and orthopaedic status (spine, hips, and joints). Prolonged fasting should be avoided, particularly in the acutely ill infant with SMA.