Spinal muscular atrophy (SMA) is a neuromuscular disorder that causes progressive muscle weakness and atrophy, eventually leading to paralysis. Classically, this is caused by mutations in the survival motor neuron 1 (SMN1) gene that drive the degeneration of alpha motor neurons in the spinal cord. 

One of the challenges physicians face with this disease is characterizing its features in each patient, ie, the rate and severity of disability progression. This is because there is great heterogeneity in the clinical presentation of affected patients. 

“Children with SMA present at different ages with a wide spectrum of clinical severity,” Nicolau and colleagues wrote in Seminars in Pediatric Neurology.


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A Variety of Phenotypes

However, there are known variants of SMA that differ in terms of clinical severity. SMA type 1 accounts for almost half of cases; it is hence the most common form of SMA from an epidemiological standpoint. Affected children develop hypotonia, as well as motor and feeding difficulties, by 6 months of age. Unfortunately, children with SMA type 1 never achieve the ability to sit independently. 

Read more about SMA prognosis 

SMA type 2 is less severe. Symptoms manifest between 6 and 18 months. These patients can sit independently, but never achieve the ability to walk. Unlike SMA type 1, in which survival rates are only a few years at best, most patients with SMA type 2 survive into adulthood. 

SMA type 3 is even less severe. Patients are typically able to walk at some point during childhood, but the clinical phenotype in other areas can vary drastically. SMA type 4 is very mild, but also the least common subtype of SMA. 

A tranche of innovative therapy has become available in recent years to treat SMA. Among them are disease-modifying treatments, such as nusinersen, onasemnogene abeparvovec, and risdiplam. 

These medications have resulted in a significant improvement in the survival rates of affected individuals. As the treatment strategies for SMA become more active and aggressive, studies have indicated that the overall prognosis for patients with SMA has improved. 

This news should be greeted with cautious relief: new therapies that allow patients to live longer can often shine a harsh spotlight on how little we know about a disease, especially when treatment plans in the past have leaned palliative in nature. Hence, the medical literature surrounding SMA needs to continuously expand if we are to keep up with existing therapeutic advancements. 

Disease-Specific Data 

Recognizing this need, De Amicis and colleagues conducted a study to characterize growth rates in children with SMA. 

“Although the use of standard growth charts has been suggested for monitoring longitudinal growth in SMA children, the clinical assessment of their growth and nutritional status would be improved by the availability of disease-specific growth percentiles curves,” they wrote. “This will also allow evaluation of the effects of the increasingly available novel disease-modifying treatments on growth and nutritional status.” 

The research team recruited patients from 5 different Italian SMA referral centers between April 2015 and May 2018. The recruited patients had to have a genetic confirmation of 5q-autosomal recessive SMA and a confirmed diagnosis of SMA type 1 or 2 and be under the age of 12 years. They had to be managed clinically according to the best supportive care practices as outlined in the Consensus Statement for Standard of Care in SMA.

The authors of the study successfully recruited 133 children with SMA type 1 and 82 children with SMA type 2. The participants underwent anthropometric measurements to assess body weight and supine length. 

At the end of the study, researchers were able to create percentile curves of weight, supine length, and body mass index (BMI)-for-age for girls and boys with SMA types 1 and 2. 

Read more about SMA treatment 

The researchers reported a few key findings. First, this was the first attempt to provide growth curves from a big, well-characterized sample of treatment-naïve patients with SMA type 1 or 2. Second, the weight of patients with SMA type 1 is significantly lower than for healthy peers in both sexes and at all ages when using WHO percentiles as a point of reference. However, the researchers also noted that children with SMA type 1 had an above-average supine length compared to the control.

“Our findings confirm that BMI references based on the general pediatric population are not good indicators of the nutritional status in SMA children as they show a growth pattern which is specific to the condition,” De Amicis and colleagues wrote. 

This is because while fat mass is proportionally higher in patients with SMA type 1 or 2, their total fat-free mass and lean mass are significantly lower compared to the control.

The main purpose of having disease-specific growth percentiles curves is to allow nutritional management in children with SMA to be optimized. This study contributes to our understanding of how children with SMA type 1 or 2 grow in comparison to their healthy peers.

“The increase in the knowledge on nutritional aspects of patients with SMA is crucial for the appropriate management of patients,” they concluded. It is indeed important for our patients that we continue to keep an open mind to broaden perspectives on the disease and improve quality of life. 

References

De Amicis R, Baranello G, Foppiani A, et al. Growth patterns in children with spinal muscular atrophyOrphanet J Rare Dis. 2021;16(1):375. doi:10.1186/s13023-021-02015-9

Nicolau S, Waldrop MA, Connolly AM, Mendell JR. Spinal muscular atrophySemin Pediatr Neurol. 2021;37:100878. doi:10.1016/j.spen.2021.100878