A group of researchers recently examined the fascinating link between spinal muscular atrophy (SMA) and defective fatty acid metabolism. They published their literature review in Brain Science. We will take a closer look at some of their findings in this article. 

SMA is a devastating neuromuscular disorder that predominantly affects children. This is because the phenotype of this disease is so severe that most patients do not make it past the first year of life. Typically, SMA causes extreme muscle wasting, hypotonia, and hyporeflexia, which results in death. 

Read more about SMA epidemiology

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If we were to measure body mass index (BMI) in patients with SMA, most of them would be classified as normal or underweight. However, when more stringent anthropometric criteria are imposed, there appears to be a trend towards increased adiposity in the SMA population. Interestingly, while BMI parameters may often be normal, further investigation reveals that patients with SMA tend to have 20% more fat when matched with healthy counterparts according to age and sex. 

In a study of 25 children, 10 participants (40%) had a fat mass index (FMI) >85th percentile that indicated “at risk of overweight,” while 5 participants (20%) had an FMI >90th percentile indicating “overweight.” This is in accordance with the Centers for Disease Control and Prevention (CDC) weight classifications. Besides demonstrating, yet again, the inadequacies of BMI in measuring fat percentage, it also raises a puzzling question – why do SMA patients tend to have increased fat mass? 

One possible theory simply looks at the disease progression of SMA. In SMA, patients get progressively weaker to the point that they are no longer able to be mobile independently. This naturally creates an imbalance between dietary intake and energy expenditure. Scientists have struggled to identify the ideal dietary regime for patients with SMA because it appears that they can suffer from being malnourished from being underfed or overfed. Moreover, motor capabilities differ greatly depending on the stage of the disease, which further complicates the efforts of dietitians to create a general dietary plan for patients with SMA. 

Yes, the curious increase in fat percentage among SMA patients can be blamed squarely on a lack of understanding of how to balance dietary requirements. However, scientists have also begun to openly speculate that there could be a more profound metabolic factor at work here. It could be that defects in fat metabolism disrupt the whole-body homeostasis of patients with SMA. This is certainly worth a discussion. 

Evaluating SMA and Defective Fat Metabolism

Let us examine the existing literature to see if any studies regarding SMA and defective fat metabolism have been investigated. An important study that we will look into involved 14 patients with SMA. The patients demonstrated high dicarboxylic aciduria, high urinary acylcarnitine excretion, and carnitine deficiency in both serum and muscle. In addition, the patients had a deficiency in acyl-coenzyme A (CoA) dehydrogenase, a vital enzyme in beta oxidation. 

Aciduria of small to medium fatty acids was more commonly observed in patients with SMA type I than in those with types II and III. This suggests that metabolic abnormalities differ according to SMA severity. In addition, 5 patients with SMA (including types I, II, and III) offered muscle biopsies for further analysis of fatty acid oxidation. The results unanimously showed: 

  • Normal enoyl-CoA hydratase activity
  • Decreased long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity
  • Decreased short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) activity
  • Decreased 3-ketothiolase activity
  • Decreased acetoacetyl-CoA activity

This means that 4 of the 5 main enzymes involved in beta oxidation are reduced in SMA across all severities. 

Read more SMA etiology

Studies have also shown that the fatty dicarboxylic acid (DCA):ketone ratio in infantile SMA bears striking resemblance to that of patients with known fatty-acid oxidation defects. In addition, this study supports the hypothesis that metabolic dysfunction can, in fact, reflect SMA severity (to a point) –  the DCA:ketone ratios for children with severe SMA who were under 10 months of age were decidedly abnormal, while infants with SMA type II of a similar age had ratios that were within acceptable normal limits. 

What Now?

Existing literature supports the idea of an association between defective fatty acid oxidation and SMA. As future research undoubtedly elucidates this link more clearly, what should healthcare professionals do in the meantime? 

The biggest implication of this association is whether dietary guidelines for patients with SMA should change. It should be noted that detailed dietary advice is currently available for patients with severe SMA who have lost the ability to swallow properly, usually with the treating physician/dietitian involved in the decision-making process. 

The researchers of this study note that many patients and their families already adopt what is known as an “elemental diet,” which is a diet that is amino acid-based and low in fat. It is believed that this kind of diet helps with digestion, especially if gut motility is slow. However, as the researchers of this study point out, “It is important to note, however, that diets that are low in fat, such as elemental diets, are at risk of being deficient in essential fatty acids and may require particular attention to ensure an adequate intake of all nutrients and essentials acids.” 

Furthermore, studies involving patients on an elemental diet showed that more than a quarter of them lacked vitamins, especially fat-soluble ones (vitamins A, D, E, and K). 

Admittedly, dietary recommendations are exceedingly difficult to make on a general basis when there are so many moving parts that may render part of the advice redundant. For example, studies have shown that some patients with SMA suffer from glucose metabolism defects. Others, at the final stages of the disease, will find it challenging to swallow anything at all. This means that, for now, highly personalized care must be given to each SMA patient with regards to dietary advice. 

Future studies should take into consideration the fact that “both the severity of disease and age critically impact fatty acid metabolism defects in SMA patients,” according to the authors of this study. This might be useful when deciding on a set of national guidelines for patients with SMA. 

If we are to give patients with SMA the care they deserve, it will inevitably mean providing them with sound nutritional guidelines as well. Future research has big shoes to fill in this regard. 


Watson KS, Boukhloufi I, Bowerman M, Parson SH. The relationship between body composition, fatty acid metabolism and diet in spinal muscular atrophyBrain Sci. 2021;11(2):131. doi:10.3390/brainsci11020131

Kolb SJ, Kissel JT. Spinal muscular atrophyNeurol Clin. 2015;33(4):831-846. doi:10.1016/j.ncl.2015.07.004