Effects of MNT on SMA.docx

Running head: EFFECTS OF MNT ON SMA SURVIVAL RATES 1
Effects of Medical Nutrition Therapy on Spinal Muscular Atrophy Survival Rates
Luisa Hammett, Kelly Karpen, Kristin Althoff, Katie Barnes, Mary Margaret J. Enrile
Southern Regional Medical Center

EFFECTS OF MNT ON SMA SURVIVAL RATES 2
Effects of Medical Nutrition Therapy on Spinal Muscular Atrophy Survival Rates
Spinal Muscular Atrophy (SMA) is one of the most common disorders of early childhood
that occurs in 1 out of every 6,700 births. This autosomal recessive motor neuron disease results
from the deletion of the survivor motor neuron gene on chromosome 5q13. A diagnosis is made
through muscle biopsies and electrophysiological evidence of denervation of intact neurons.
SMA is broken down further into four main clinical subtypes. Criteria for classification include
age of onset and highest motor-related milestone achieved. The most severe subtype is SMA
Type I, which will be the focus of this report.
The typical age of onset for SMA Type I is 6 months or younger. Children with this type
of SMA do not develop the muscle strength or motor control to be able to sit up independently,
and most die before age two. The typical route of progression for SMA is increasing muscle
weakness, dysphagia, aspiration, and death. SMA Type II is characterized by the ability to sit
independently with an age of onset between six to eighteen months. Children with SMA Type III
have an age of onset greater than eighteen months, the ability to walk about twenty-five steps,
and an indefinite life expectancy. Lastly, children with SMA Type IV have the ability to walk
normally, an age of onset of greater than five years, and an indefinite life expectancy.
Since SMA, particularly Type I, is such a devastating disease, several studies have been
conducted to determine interventions that can improve quality and/or prolong life expectancy.
One of the major concerns that arise from the muscle weakness SMA patients experience is the
inability to chew and/or swallow properly, which puts them at high risk for aspiration that can
lead to pneumonia and death; therefore, most studies on SMA have been focused on respiratory
and nutritional interventions.

Complications from SMA are not limited to motor dysfunction and muscle wasting.
Patients also experience metabolic abnormalities, specifically glucose and fatty acids, as well as
decreased bone density. A study by Bowerman et. al. (2012) found glucose abnormalities in 3
out of 6 children with SMA after autopsies were performed. Children with SMA also tend to
have an elevated level of alpha cells, which produce glucagon, and abnormally low levels of beta
cells, which secrete insulin. Due to limited mobility, children with SMA are more likely to
become obese and have decreased lean body mass. This can lead to increased risk for glucose
metabolism abnormalities. In regards to bone health, a study by Shanmugarajan et. al. (2009)
found that mice with SMA had low bone density, high bone turnover, and enhanced osteoclast
formation. Further studies are needed to gain a better understanding on the effect of SMA on
bone health in humans.
All of the conditions mentioned above have the potential to be influenced by nutritional
intervention. This raises the question of whether Medical Nutrition Therapy (MNT) practices
increase survival rates in patients with SMA. Several studies have suggested that MNT plays a
significant role in the management of SMA. One study in mice indicated that maternal diet may
play a role in the phenotype of SMA developed in offspring, and can have an effect on life
expectancy as well (Butchbach et al., 2009). Researchers found that a high fat maternal diet in
mice with SMA resulted in a 21% increase in lifespan when compared to a high carbohydrate,
low fat diet. Studies in humans are necessary to determine whether modification of maternal diet
yields similar results to that of mice; however, such studies would be difficult to perform as
genetic testing would likely be necessary to determine which mothers are likely to give birth to
children with SMA.

Several studies (Bowerman et. al., 2012; Butchbach et al., 2009; Shanmugarajan et. al.,
2009) have shown that early nutrition intervention is the key to increasing longevity and
reducing complications related to SMA. Nutrition intervention in SMA generally refers to a
gastrostomy tube since children with SMA have difficulty chewing and swallowing, therefore
leading to difficulty obtaining adequate nutrition via the oral route (Davis et al., 2014). By
proactively providing SMA patients with feeding tubes, the risk of inadequate nutrient intake and
aspiration are greatly reduced, which, in theory, can add to life expectancy. Adequate nutrition
could also play a role in reducing the risk of the side effects mentioned earlier, such as bone loss,
hyperglycemia, and obesity.
Nutrition and dietetics programs generally do not cover the study of SMA nutrition
management, but the need for its inclusion in the future is becoming greater. The probability of
registered dietitians (RDs) encountering SMA patients in clinical settings is increasing as
children with the most severe form of SMA are living longer due to advancements in medical
and nutritional management of the disease. An interdisciplinary approach to care is crucial in the
medical treatment of children with SMA. According to Godshall and Wong (2012), a healthcare
team consisting of a “pulmonologist, neurologist, gastroenterologist, geneticist, social worker,
registered dietitian, physical therapist, occupational therapist, speech and language pathologist,
endocrinologist and/or cardiologist” (p.1-2) is crucial in providing effective overall care for the
patient. One of the other top priorities in providing care for SMA patients is managing the
nutritional consequences of the disease related to “decreased lean body mass and increased fat
mass, gastrointestinal dysmotility, bulbar dysfunction, dysphagia, osteoporosis, and metabolic
abnormalities consistent with a secondary fatty acid oxidation disorder” (Davis et al., 2014,
p.1467). The following should be evaluated when considering the nutritional status of children

with SMA: weight, growth patterns, diet history, diet nutrient analysis, feeding practices, and lab
analysis of their “serum proteins, 25-hydroxyvitamin D, serum amino acids, essential fatty acids,
and carnitine” (Davis et al., 2014. p. 1469).
There has been a positive trend in survival rates of patients with SMA, but the trend
cannot be ascribed to any single factor. As mentioned before, it is likely that medical and
technological advances in pulmonary care along with aggressive nutritional support have played
an important role (Mannaa et al., 2009). A study conducted by Poruk et al. (2012) is consistent
with Mannaa et al.’s (2009) findings in which rates of SMA type I survival are surpassing the
age of two due to the significant role nutrition plays in both the quality of life and survival rates
for children with SMA.
Pulmonary Complications
According to Mannaa et al. (2009), respiratory difficulties related to weakening of the
intercostal muscles are prevalent in SMA regardless of type. Deteriorating of the muscles used
for inspiration and expiration cause pulmonary issues seen in type I and II including labored
breathing and a weak cough. Increased work of breathing can cause oxygen desaturation with
feedings, and also increase energy expenditure. Without respiratory support, infants with SMA
type I rarely live past the age of two.
In an observational study done at Cincinnati Children’s Hospital Medical Center, patients
with the most severe form of SMA have the shown the most increase in survival rates in the last
two decades, which can be attributed to nutrition support along with advancements in respiratory
care. Nutrition plays an enormous role to reduce the risk of increased respiratory problems and
improving quality of life. Nutrition intervention can aid in alleviating issues related to the
malnutrition often associated with respiratory complications. Dyspnea resulting from respiratory

dysfunction can make oral intake more strenuous leading to decreased appetite and consumption.
Inadequate nutrient consumption can further worsen overall nutrition and respiratory status. Both
of these combined with diminished immunological responses related to malnutrition can lead to
even more severe consequences like chest infections. This further solidifies the importance of
medical nutrition therapy and the role RDs can play in preventing and/or improving SMA
complications related to nutrition.
Swallowing difficulties
Muscle weakness is evident by six months of age in patients with SMA type 1. These
affected infants never achieve the ability to sit unsupported. In an observational study consisting
of a nutritional and medical history survey of children with SMA type 1, all subjects depended
on a feeding tube for essential energy intake. The average age of placement was eleven months
of age (Davis et al., 2014). There is a relationship between bulbar dysfunction and progressive
respiratory dysfunction and chewing and swallowing difficulties. Bulbar dysfunction has also
been reported in SMA type II (Chen et al., 2012, p. 450).
A cross sectional study analyzing the prevalence and risk factors for feeding and
swallowing difficulties in SMA type II and III found that the patients who required respiratory
management had significantly more feeding and swallowing difficulties than those who did not
(Chen et al., 2012, p. 450). Of all the patients studied, nearly half (44.4%) had at least one
chewing and swallowing difficulties. The most prevalent chewing and swallowing difficulties
were choking, difficulty conveying food to the mouth and chewing difficulties. Nutrition
interventions in these patients included dietary modification and nasogastric tube feeding. Of
these patients, those with difficulty chewing and swallowing had higher rates of underweight
than those without these problems.

Gastrointestinal Complications
Children with SMA type I and II also often face gastrointestinal difficulties, such as
delayed stomach emptying, constipation, abdominal distention, bloating, and gastroesophageal
reflux. This is especially dangerous for children with SMA type I who do not have the ability to
sit upright. Risk of aspiration from gastroesophageal reflux and vomiting can lead to pneumonia
and often death. In the observational study of nutritional and medical history of children with
SMA type 1, half (23 of 44) of the subjects reported having formula tolerance issues including
gastrointestinal pain, increased reflux, emesis, and poor gastric emptying. Gastroesophageal
reflux was commonly reported and a majority of the subjects had a Nissen Fundoplication
procedure to prevent reflux. A majority also reported using elemental formulas, probiotics and
bowel regulating agents (Davis et al., 2014).
Fasting
In an observational study done at Cincinnati Children’s Hospital Medical Center, positive
trends were found between SMA patient survival and vigorous pulmonary and nutrition care
(Mannaa et al., 2009). In prolonged periods of fasting, over 6-8 hours, the muscle becomes the
primary source of glucose. In order to maintain blood glucose, the body will degrade as much
muscle as needed. This use of muscle in times of fasting may lead to additional weakening of
already atrophied muscle in a patient with SMA (Mannaa et al., 2009). The goals of nutritional
support in patients with SMA are to limit fasting to prevent muscle protein breakdown and to
ensure adequate amounts of dietary protein to enhance protein synthesis by muscle.
Metabolic Complications
According to Poruk et al. (2012), abnormalities in the metabolism of fatty acids seen in
children with SMA has been shown to have detrimental effects on their overall metabolism,

especially with Type I and II. The exact mechanism of the fatty acid metabolism abnormality in
SMA is unknown, but is suspected to be related to the severity of SMA related to the loss of
survival motor neuron function. Previous reports have indicated a potential need for closer
attention to limiting fat intake. “The intolerance of fat in some patients has led to an increasing
number of children with SMA on low fat diets similar to those used in children with inborn
errors of fatty acid oxidation” (Poruk et al., 2012, p. 966). However, a consensus has not been
achieved regarding limiting dietary fat intake and further research is necessary (Davis et al.,
2014).
Overweight
Excessive fat mass can cause increases in pressure on the atrophied muscles. This
pressure has a negative effect on motor function and can lead to increased morbidity related to
SMA (Sproule et al., 2009, p. 396). “A seemingly insignificant increase in body fat can impair
motor function and decrease health status in adolescent SMA patients, regardless of type”
(Sproule et al., 2009, p. 396). Although it is uncommon for SMA patients to be overweight,
careful monitoring of weight gain is crucial.
Nutrient Needs and Monitoring
When comparing healthy children versus ones with SMA, the latter tend to have lower
energy needs (Godshall and Wong, 2012), because they have their lower metabolic rate related to
lower lean body mass from muscle atrophy. Certain factors have to be examined when
calculating their energy needs, such as mechanical ventilation. Alterations to their total caloric
needs must be conducted on a gradual increments since they are greatly affected by minute
feeding modifications, which may take from days, weeks, or months. Godshall and Wong (2012)

suggests increasing the estimated daily caloric intake by three to five percent until energy goal is
met.
Children with SMA have protein, vitamin, and mineral needs that are very close to that of
healthy children; however, their reduced calorie needs can lead to inadequate micronutrient
consumption. Findings of the dietary record analysis in the observational study of caloric and
nutrient intake, bone density, and body composition in infants with spinal muscular atrophy type
I, indicate inadequate intake for a variety of nutrients in this population. Common nutrients
considered at greater risk of deficiency in this cohort includes: alpha-linoleic fatty acid, linoleic
fatty acid, vitamin A, vitamin D, vitamin E, vitamin K, folate, calcium, iron, and magnesium.
Vitamin D
SMA Type I patients are at an increased risk for vitamin D deficiency. Their poor intake,
compounded by limited sun exposure because of heat intolerance, limited absorptive capacity,
and drug-nutrient interactions are all factors that decrease serum 25-hydroxy vitamin D levels.
(Aton et al., 2013). Vitamin D status plays a role in bone mineral density; therefore, inadequate
vitamin D intake could place patients with SMA at an increased risk for osteoporosis and bone
fractures. In the observational study of vitamin D intake in SMA type I patients, 75% of the
subjects had inadequate vitamin D intakes initially. This observational study had a small subset
of subjects; thus, further studies are needed to help determine appropriate intakes for vitamin D
and other nutrients in this population (Aton et al., 2013).
Nutrition plays an important role in the quality of life and outcome of patients with spinal
muscular atrophy. Survival has increased among patients born in 1995 through 2006 when
compared to those born in 1980 through 1994 and shown that gastrostomy tube feeding was one
significant factor contributing to the reduction in risk of death (Oskoui et al., 2007).

Nutrition management in SMA is necessary to achieve adequate growth, to help with
motor function and respiratory status, and to assist with illness prevention and recovery. It is
encouraged and considered vital that when dealing with patients with SMA that an assessment is
done in regards to feeding and nutritional needs. The majority of infants and babies with SMA
can be adequately managed nutritionally with nasogastric feeding but it may be considered to
pursue gastrostomy for some infants if the benefits outweigh the risks (Roper et al., 2009). Main
areas of nutritional concern that may impact the quality of life and outcome of the patients seem
to encompass obesity, vitamin D, protein and fat intake, and safe intake of nutritional needs.
Despite its importance, there is a very little evidence-based research to support specific
recommendations for dietary management. Currently, most spinal muscular atrophy patients do
not have access to a registered dietitian, which places the burden on parents and physicians to
make decisions without clear evidence to guide them (Aton et al., 2013). Connecting these SMA
patients with registered dietitians for assessment and nutritional guidance could be a crucial step
towards nutritional advancement and research opportunities. Working with parents of these
children through surveys have also shown to provide useful data in regards to taking into
consideration clinical responses to treatment, creating standard of care guidelines, and assisting
to effectively design clinical trials (Finkel et al., 2008). Overall, further outcome data and
research is needed in the area of nutrition management of children with SMA, particularly of
those with type I.

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