SMA Associated With Metabolic, Nutritional Issues

With emerging evidence suggesting that the impact of survival motor neuron (SMN) deficiency extends past motor neurons in patients with spinal muscular atrophy (SMA), researchers analyzed the latest data on metabolic and nutritional issues associated with the condition.

Documented issues include lipid metabolic abnormalities, glucose metabolic abnormalities, and altered vitamin levels.

“Active nutrition support and metabolism surveillance are crucial for patients with SMA, and a comprehensive nutritional assessment could guide individualized nutrition therapy for this vulnerable population,” commented the researchers. “With the emergence of new gene-targeted and disease-modifying therapies, which may affect the metabolism of SMA patients, personalized nutritional optimization may become particularly important.”

The most commonly studied nutritional issue in SMA is dysregulated lipid metabolism, with abnormal levels of fatty acid oxidation metabolites—particularly dicarboxylic aciduria and esterified carnitine—detailed in several studies of patients with severe SMA type. Since these first reports, subsequent research has indicated that the condition likely causes metabolic defects involving fatty acid metabolism.

According to the researchers, there have been several serum fatty acids and lipids identified as correlated to motor function in SMA, which may have the potential to be leveraged as biomarkers in the condition.

Additional findings on altered lipid metabolism include:

• Increased urine dicarboxylic acids in both fed and fasting states, especially in the longer-chain (C10 and C22) 3-hydroxydicarboxylic acids, in a 9-month-old patient with SMA type 1
• Abnormal excretion of ethylmalonic acid from urine organic acids, reduced carnitine levels in serum, and increased excretion of urinary acylcarnitines across 14 patients with SMA type 2
• Reductions in muscle mass, physical stress, and defects in fatty acid metabolism may cause hypoglycemia and non-diabetic ketoacidosis, according to a case report of a patient with SMA type 2

Several case studies and cross-sectional studies also highlighted an altered glucose metabolism in patients with SMA. Hypoglycemia was found across patients, explained in some cases by “reduced muscle protein, leading to lower availability of amino acids (alanine) as substrates for gluconeogenesis in the liver.”

The researchers noted that there have been indications among patients receiving SMN restoration therapy that it may increase the risk of pancreatic and glucose metabolism defects, suggesting the need for close monitoring of glucose homeostasis in patients to better determine the role of SMN in glucose metabolism and pancreatic function.

SMA has also been reported to impact levels of vitamin E, vitamin K, folate intakes, vitamin D, and calcium.

“The SMN protein may play an active role in bone remodeling or uptake of vitamin D and calcium; therefore, patients with SMA are often accompanied by osteopenia and may contend with fractures due to minor injuries,” said the researchers, writing that suboptimal vitamin D intake is often observed in patients with SMA. 

“Compared with other neuromuscular disorders, reduced bone mineral density seems more significant in patients with SMA, especially in those losing ambulatory function.”

Reference: Li Y, Chen T, Wu Y, Tseng Y. Metabolic and nutritional issues associated with spinal muscular atrophy. Nutrients. 2020;12(12):3842. doi:10.3390/nu12123842