Being a genetic disorder with no cure yet found, spinal muscular atrophy (SMA) treatment relies on the management of symptoms and reduction of discomfort in patients. Considering SMA-associated risk factors and long-term health complications that may arise are crucial for the improvement of quality of life and patient’s prognosis.
Sedentary Lifestyle and Orthopedic Factors
As SMA is a neuromuscular degenerative disorder, patients with this disease commonly experience motor weakness and impaired mobility that predisposes them to several musculoskeletal issues and pressure ulcers,1,2 often associated with wheelchair and/or bed rest use. To prevent early deterioration of motor capacity and to improve the quality of life of patients with SMA, early recognition and proper management are essential. Physical therapy is key in managing orthopedic issues and preventing a sedentary lifestyle and will maximize endurance and fitness by including activities such as swimming, aquatic therapy, and adaptive sports.2 Stretching and bracing programs are also used to preserve flexibility and prevent contractures, which are common in nonambulatory individuals.2,4
Another orthopedic complication observed in almost all individuals with SMA 1c and 2 and in half of those persons with SMA 1 and 3 is scoliosis,1 which when left untreated, leads to chest-cage deformities and consequent respiratory complications5 and decreased cardiac output.6 In fact, reports demonstrated that nearly 50% of children with SMA develop spinal curvatures that require surgery before age 10 years.1 Moreover, as the disease progresses, nonambulatory individuals can also develop thoracic kyphosis.7
Because of compromised mobility, fractures also are associated risks for patients with SMA. A previous report has shown that 9.3% of 93 patients with SMA 1, 2, or 3 have had previous fractures, predominantly fractures of the femur and humerus bones,8,9 which result from general falls and/or falls from the wheelchair.
Respiratory failure is most often the cause of death in SMA 1 and 2.1,2 The progressive impairment of the pulmonary function together with weakness of the respiratory muscles, reduction of the chest wall, lung compliance, and alveolar multiplication lead to this failure in respiratory function.1,6 This impairment results in weak cough, with inappropriate clearance of secretions, increasing risk for aspiration, hypoventilation during sleep, and persistent pulmonary infections, such as pneumonia,1,2,10 To improve respiratory insufficiency and to decrease the risk of developing these complications, noninvasive ventilation, such as bilevel positive airway pressure and airway clearance techniques, are frequently used.11–13
Associated with respiratory infections are the prevalence of feeding and swallowing difficulties (dysphagia), which commonly leads to choking (a prevalence of 30.6%14) and aspiration that can be life-threatening.10,14 Identifying risk factors for feeding and swallowing difficulties is important because of its high frequency and because of its associated problems, such as pneumonia and other pulmonary complications,14, which can also increase the risk for infections.15-17 In type 2 SMA, the more common risk factors associated with feeding and swallowing difficulties were sitter and nonsitter status, respiratory management needs, and poor head control.14 Unexpectedly, motor function was an independent risk factor for feeding and swallowing complications in patients with type 2 and 3 SMA.14
Nutritional and Metabolic Factors
Gastrointestinal complications such as constipation, delayed gastric emptying, and gastroesophageal reflux with aspiration — which can be potentially life-threatening, are often observed in individuals with SMA1. However, the reason for such problems remains to be understood, as it is not clear whether they result from immobility and nutritional deficits or from an impairment in gastrointestinal motility itself.18,19 Gastroesophageal reflux, delayed gastric emptying, and constipation are often observed in patients who do not sit or stand, and are less prevalent in ambulatory patients with SMA.2
Gastrointestinal dysfunction is also a result of feeding and swallowing difficulties because of bulbar dysfunction, universal to all patients with SMA type 1, which can also lead to nutritional problems.2 To manage malnutrition, particularly in infants with SMA type 1, a gastrostomy and laparoscopic Nissen fundoplication, which, in particular, improves survival, is suggested.20,21
Poor nutrition can be another serious problem for individuals with SMA, and apart from the placement of a gastrostomy tube, periods of fasting should be avoided, as it will contribute to further muscle weakness and consequent impaired function.1,2 In contrast, nonambulatory patients with SMA type 2 and 3 are at risk of developing obesity.7,22 To control and manage risk of obesity, a dietitian should follow each patient to promote a healthy nutrition and growth curve and to help patients avoid excessive caloric intake.2 In addition, supplemental intake of vitamin D and calcium should be advised, as there is a predisposition for a decline in bone mineral density with age.23
As mentioned, prolonged fasting should be avoided in individuals with SMA, as it increases the risk for metabolic abnormalities. Severe metabolic acidosis, with dicarboxylic aciduria and low-serum carnitine concentrations, is an inexplicable complication of SMA.1,24 Its mysterious nature relies on the fact that it is still unclear whether such metabolic deviations are a cause or a consequence of the disorder. Nevertheless, a report in 2012 suggested that glucose metabolism and pancreatic defects may play a role in SMA pathogenesis.25 Recent studies demonstrated an abnormal fatty acid metabolism26 and other metabolic-associated issues in the disease.27
Reviewed by Michael Sapko, MD on 7/1/2021
- Prior TW, Leach ME, Finanger E. Spinal muscular atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle; 2000.
- Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clin. 2015;33(4):831-846. doi:10.1016/j.ncl.2015.07.004
- Fujak A, Kopschina C, Gras F, Forst R, Forst J. Contractures of the lower extremities in spinal muscular atrophy type II. Descriptive clinical study with retrospective data collection. Ortop Traumatol Rehabil. 2011;13(1):27-36. doi:10.5604/15093492.933792
- Wang HY, Ju YH, Chen SM, Lo SK, Jong YJ. Joint range of motion limitations in children and young adults with spinal muscular atrophy. Arch Phys Med Rehabil. 2004;85(10):1689-1693. doi:10.1016/j.apmr.2004.01.043
- Haaker G, Fujak A. Proximal spinal muscular atrophy: current orthopedic perspective. Appl Clin Genet. 2013;6(11):113-120. doi:10.2147/TACG.S53615
- Chng SY, Wong YQ, Hui JH, Wong HK, Ong HT, Goh DY. Pulmonary function and scoliosis in children with spinal muscular atrophy types II and III. J Paediatr Child Health. 2003;39(9):673-676. doi:10.1046/j.1440-1754.2003.00266.x
- Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103-115. doi:10.1016/j.nmd.2017.11.005
- Granata C, Giannini S, Villa D, Bonfiglioli Stagni S, Merlini L. Fractures in myopathies. Chir Organi Mov. 1991;76(1):39-45.
- Vestergaard P, Glerup H, Steffensen BF, Rejnmark L, Rahbek J, Moseklide L. Fracture risk in patients with muscular dystrophy and spinal muscular atrophy. J Rehabil Med. 2001;33(4):150-155.
- Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. doi:10.1177/0883073807305788
- Panitch HB. The pathophysiology of respiratory impairment in pediatric neuromuscular diseases. Pediatrics. 2009;123 Suppl:S215-8. doi:10.1542/peds.2008-2952C
- Markström A, Cohen G, Katz-Salamon M. The effect of long term ventilatory support on hemodynamics in children with spinal muscle atrophy (SMA) type II. Sleep Med. 2010;11(2):201-204. doi:10.1016/j.sleep.2009.08.014
- Nickol AH, Hart N, Hopkinson NS, Moxham J, Simonds A, Polkey MI. Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation. Thorax. 2005;60(9):754-760. doi:10.1136/thx.2004.039388
- Chen Y-S, Shih H-H, Chen T-H, Kuo C-H, Jong Y-J. Prevalence and risk factors for feeding and swallowing difficulties in spinal muscular atrophy types II and III. J Pediatr. 2012;160(3):447-451.e1. doi:10.1016/j.jpeds.2011.08.016
- Mannaa MM, Kalra M, Wong B, Cohen AP, Amin RS. Survival probabilities of patients with childhood spinal muscle atrophy. J Clin Neuromuscul Dis. 2009;10(3):85-89. doi:10.1097/CND.0b013e318190310f
- Gormley MC. Respiratory management of spinal muscular atrophy type 2. J Neurosci Nurs J Am Assoc Neurosci Nurses. 2014;46(6):E33-E41. doi:10.1097/JNN.0000000000000080
- Deguise M-O, Kothary R. New insights into SMA pathogenesis: immune dysfunction and neuroinflammation. Ann Clin Transl Neurol. 2017;4(7):522-530. doi:https://doi.org/10.1002/acn3.423
- Karasick D, Karasick S, Mapp E. Gastrointestinal radiologic manifestations of proximal spinal muscular atrophy (Kugelberg-Welander syndrome). J Natl Med Assoc. 1982;74(5):475-478.
- Ionasescu V, Christensen J, Hart M. Intestinal pseudo-obstruction in adult spinal muscular atrophy. Muscle Nerve. 1994;17(8):946-948. doi:10.1002/mus.880170816
- Durkin ET, Schroth MK, Helin M, Shaaban AF. Early laparoscopic fundoplication and gastrostomy in infants with spinal muscular atrophy type I. J Pediatr Surg. 2008;43(11):2031-2037. doi:10.1016/j.jpedsurg.2008.05.035
- Yuan N, Wang CH, Trela A, Albanese CT. Laparoscopic Nissen fundoplication during gastrostomy tube placement and noninvasive ventilation may improve survival in type I and severe type II spinal muscular atrophy. J Child Neurol. 2007;22(6):727-731. doi:10.1177/0883073807304009
- Sproule DM, Montes J, Montgomery M, et al. Increased fat mass and high incidence of overweight despite low body mass index in patients with spinal muscular atrophy. Neuromuscul Disord. 2009;19(6):391-396. doi:10.1016/j.nmd.2009.03.009
- Kinali M, Banks LM, Mercuri E, Manzur AY, Muntoni F. Bone mineral density in a paediatric spinal muscular atrophy population. Neuropediatrics. 2004;35(6):325-328. doi:10.1055/s-2004-830366
- Kelley RI, Sladky JT. Dicarboxylic aciduria in an infant with spinal muscular atrophy. Ann Neurol. 1986;20(6):734-736. doi:10.1002/ana.410200615
- Bowerman M, Swoboda KJ, Michalski J-P, et al. Glucose metabolism and pancreatic defects in spinal muscular atrophy. Ann Neurol. 2012;72(2):256-268. doi:10.1002/ana.23582
- Deguise M-O, Baranello G, Mastella C, et al. Abnormal fatty acid metabolism is a core component of spinal muscular atrophy. Ann Clin Transl Neurol. 2019;6(8):1519-1532. doi:https://doi.org/10.1002/acn3.50855
- Li Y-J, Chen T-H, Wu Y-Z, Tseng Y-H. Metabolic and nutritional issues associated with spinal muscular atrophy. Nutrients. 2020;12(12):3842. doi:10.3390/nu12123842