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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