Spinal Muscular Atrophy (SMA)


Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by defects in the survival motor neuron 1 (SMN1) gene, which leads to selective destruction of the alpha neurons of the anterior horn cells of the spinal cord and brainstem.1,2 Clinical features include progressive muscle atrophy and weakness, resulting in swallowing and feeding complications, which have a significant impact on the nutritional state of these patients.3,4

Patients with SMA, which has no cure, typically achieve a better quality of life through physical therapy, posture management, and, among other things, nutritional support.4 In fact, providing individualized nutrition, especially in children, is essential for improving the quality of life of patients with SMA,3 with clinicians playing a critical role in formulating a good diet for patients with the disease.

Science of Dietary Intake

Regarding dietary intake, 2 studies have demonstrated a positive correlation among vitamin D, calcium and magnesium intake, and bone mineral density in patients with SMA.5,6 Vitamin D intake was insufficient in 75% of individuals with SMA type 16 and 36.7% of persons with SMA type 2 or 3.7 These findings suggest that vitamin D, calcium, and magnesium supplementation may be required in many patients.

Recent studies have also shown that children with SMA may be at risk for micronutrient deficiencies such as alpha-linolenic fatty acid, linoleic fatty acid, vitamin A, vitamin D, vitamin K, folate, calcium, iron, and magnesium.3

Variations in macronutrient intake and utilization occur in individuals with SMA. Data have shown aberrant fat distribution and fatty acid metabolism dysfunction in this disorder.8

Data using different mouse models of SMA have established a correlation between lifespan and the different components of the maternal diet, whereas increasing the content of fat affected lifespan, extending the average lifespan by 25%9. More recently, studies have provided evidence that low-fat diets nearly double survival in a mouse model of SMA.10 These 2 studies have contradictory outcomes: one favors high-fat content whereas the other shows improvement with a low-fat diet. Although it is difficult to conclude which type of diet should be recommended to be used in patients with SMA, these findings still need clinical proof, and there is still no evidence in humans of a direct effect on disease progression.

In terms of dietary allowances for energy, protein, and fat, one study demonstrated that children with SMA type 1 did not meet the recommended standards and that, in fact, the intake of energy decreased with age,5 whereas others reported a 35% underfeeding and 29% overfeeding in patients.11

Fatty Acid Metabolism Considerations

Although the current dietary guideline for SMA only considers clinical features (swallowing, dysphagia, weight, gastrointestinal function, glycemic control, and bone health),12 it does not contemplate fatty acid metabolism dysfunction. Nevertheless, families and patients commonly use elemental diets.8 These types of diets are amino-acid–based and low in fat feeds.8 As elemental diets are a source of easily digestible protein, they have been shown to be beneficial in patients with a background of poor digestion whereas their low-fat content supports gastric motility and diminishes reflux.13 This is important since half of SMA type I patients present with gastric reflux.14

Some constituents of elemental diets are similar to those low-fat diets used in SMA mice studies10; however, elemental diets that are low in fat could present a higher risk of developing essential fatty acid deficiency, which should be taken into consideration and carefully managed to allow a correct intake of all nutrients and fats.8 In fact, an observational study of caloric and nutrient intake showed that the number of elemental diets supplemented with oil is greater than other diets (38% vs 15%).

Another important part of dietary intake to consider in SMA is its interaction with patient treatments, as the diet can influence the bioavailability and pharmacokinetics of drugs.15,16 Two distinct studies using mice with SMA have demonstrated that drug efficacy can be modulated depending on the type of diet that the animals are fed,9,17 suggesting the importance of the correct nutritional support.

Although to date no studies have provided an optimal dietary practice for patients with SMA, there is a clear need to better understand the impact that a fatty acid dietary intervention can have on the quality of life and nutritional management for patients with SMA.

Reviewed by Michael Sapko, MD on 7/1/2021

References

  1. Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155-165. doi:https://doi.org/10.1016/0092-8674(95)90460-3
  2. Wirth B, Herz M, Wetter A, et al. Quantitative analysis of survival motor neuron copies: Identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet. 1999;64(5):1340-1356. doi:https://doi.org/10.1086/302369
  3. Moore GE, Lindenmayer AW, McConchie GA, Ryan MM, Davidson ZE. Describing nutrition in spinal muscular atrophy: a systematic review. Neuromuscul Disord. 2016;26(7):395-404. doi:https://doi.org/10.1016/j.nmd.2016.05.005
  4. 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
  5. Poruk KE, Davis RH, Smart AL, et al. Observational study of caloric and nutrient intake, bone density, and body composition in infants and children with spinal muscular atrophy type I. Neuromuscul Disord. 2012;22(11):966-973. doi:10.1016/j.nmd.2012.04.008
  6. Aton J, Davis RH, Jordan KC, Scott CB, Swoboda KJ. Vitamin D intake is inadequate in spinal muscular atrophy type 1 cohort: correlations with bone health. J Child Neurol. 2013;29(3):374-380. doi:10.1177/0883073812471857
  7. Vai S, Bianchi ML, Moroni I, et al. Bone and spinal muscular atrophy. Bone. 2015;79:116-120. doi:10.1016/j.bone.2015.05.039
  8. Watson KS, Boukhloufi I, Bowerman M, Parson SH. The relationship between body composition, fatty acid metabolism and diet in spinal muscular atrophy. Brain Sci. 2021;11(2):131. doi:10.3390/brainsci11020131
  9. Butchbach MER, Rose FF, Rhoades S, et al. Effect of diet on the survival and phenotype of a mouse model for spinal muscular atrophy. Biochem Biophys Res Commun. 2010;391(1):835-840. doi:https://doi.org/10.1016/j.bbrc.2009.11.148
  10. Deguise M-O, Chehade L, Tierney A, Beauvais A, Kothary R. Low fat diets increase survival of a mouse model of spinal muscular atrophy. Ann Clin Transl Neurol. 2019;6(11):2340-2346. doi:https://doi.org/10.1002/acn3.50920
  11. Mehta NM, Newman H, Tarrant S, Graham RJ. Nutritional status and nutrient intake challenges in children with spinal muscular atrophy. Pediatr Neurol. 2016;57:80-83. doi:https://doi.org/10.1016/j.pediatrneurol.2015.12.015
  12. 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
  13. Horiuchi A, Nakayama Y, Sakai R, Suzuki M, Kajiyama M, Tanaka N. Elemental diets may reduce the risk of aspiration pneumonia in bedridden gastrostomy-fed patients. Am J Gastroenterol. 2013;108(5):804-810.
  14. Davis RH, Godshall BJ, Seffrood E, et al. Nutritional practices at a glance: spinal muscular atrophy type I nutrition survey findings. J Child Neurol. 2014;29(11):1467-1472. doi:10.1177/0883073813503988
  15. Rein MJ, Renouf M, Cruz-Hernandez C, Actis-Goretta L, Thakkar SK, da Silva Pinto M. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. Br J Clin Pharmacol. 2013;75(3):588-602. doi:https://doi.org/10.1111/j.1365-2125.2012.04425.x
  16. Koziolek M, Alcaro S, Augustijns P, et al. The mechanisms of pharmacokinetic food-drug interactions – a perspective from the UNGAP group. Eur J Pharm Sci. 2019;134:31-59. doi:https://doi.org/10.1016/j.ejps.2019.04.003
  17. Narver HL, Kong L, Burnett BG, et al. Sustained improvement of spinal muscular atrophy mice treated with trichostatin A plus nutrition. Ann Neurol. 2008;64(4):465-470. doi:https://doi.org/10.1002/ana.21449