Spinal Muscular Atrophy (SMA) is a congenital, progressive neuromuscular disease with the most common age of onset in early childhood.1 Childhood is a period of significant growth and development. While patients with some forms of SMA (type 0 and 1) will experience fatal complications before significant growth would be expected, patients with other forms of SMA (types 2-4) may survive to adolescence or adulthood.2
While ensuring healthy growth is a general concern in patients with congenital neuromuscular diseases, there exists no broad standardized approach for the assessment of growth in patients with any form of SMA. The Consensus Statement for Standard of Care in Spinal Muscular Atrophy explicitly stated assessment of nutrition and management of growth as specific issues relevant to all patients with SMA.3 The Consensus Statement acknowledged the growth issues across the lifetime spectrum of SMA, that patients with earlier onset SMA invariably suffer growth failure3,4 and those with later onset have diminished mobility and obesity.3,4 Finally, the Consensus Statement highlighted a need for research into defining what constituted “normal” growth in any form of SMA as research on the topic was lacking.3
Growth failure, defined as a weight below the fifth percentile or dropping two major percentiles over six months, is a nearly universal finding in patients with SMA type 1 and is found in many patients with SMA type 2 as well.5 When growth failure occurs in patients with SMA, it occurs within months of weakness with muscle loss and nearly universally within the first two years of life.5 Later age of onset of SMA increases likelihood of escaping growth failure.5 A study of patients with type 1 SMA suggests that growth failure is inevitable in many patients as a consequence of disease.6 However, surveys of patients with SMA have suggested that despite lower caloric needs than healthy peers due to decreased relative muscle mass, some patients with early onset SMA still may be undernourished.6,7 Chewing and swallowing issues in patients lacking gastrostomy tubes may underlie some of the observed malnutrition in patients with SMA type 2.8 Aggressive respiratory intervention early in SMA disease course can promote growth and development in patients with SMA type 2.9 Other data suggests that reliance on traditional assessments of growth using body mass index, body composition, or standardized growth charts are linked more to neuromuscular decompensation than nutrition and lead to the spurious conclusions of malnutrition and growth abnormalities.6,10 Instead, investigators advocate for individualized comprehensive evaluations using SMA-specific normative values7 and more accurate growth techniques evaluated in SMA patients such as noninvasive adiposity screening.11
Patients with SMA who do not experience growth failure still have many reasons for abnormal growth and confound growth assessment. Non-ambulatory patients with SMA experience high rates of obesity as a direct consequence of immobility and secondarily as the pathological loss of muscle fosters adipose replacement.12 SMA creates a feedback loop fostering obesity. As muscle mass diminishes, patients become less active, and with unchanged caloric intake, patients gain weight due to lower caloric needs which means more body mass for weaker muscles to move, etc. Nevertheless, obesity is considered a modifiable morbidity in patients with SMA.4 Simple dietary interventions can promote modest adipose weight loss in patients with SMA.13 A study of non-ambulatory patients with SMA demonstrated the seemingly paradoxical outcome that training patients to use a powered wheelchair increased their ambulation suggesting assistance devices do not promote inactivity.14 Physicians should be aware that loss of function may occur in otherwise “stable” forms of SMA in ambulatory patients as a result of growth placing increased demands on weakened muscles.15 Lean body mass is unreliable as a longitudinal biomarker in SMA as lean body mass trends lower with advanced age in patients with SMA irrespective of other factors.16 Elevations in the hormone leptin independent of body mass are apparent in many patients with SMA and suggest a previously unappreciated neurodegenerative component of SMA with significant physiological consequences on weight and growth.17
Patients with SMA have unique factors that impact growth assessment.18 Complicating matters, traditional techniques for bedside evaluation of growth and body composition in chronically ill patients may not yield accurate results and may give inaccurate assessments in SMA specifically.10,19 Patients with SMA can have evidence of high or low metabolic states, and evaluating patients with SMA on a single measurement like body mass index is inadequate to assess growth.3,7 Physicians caring for patients with SMA therefore are encouraged to approach balancing each patient’s nutrition and growth on an individualized basis18 and to utilize a comprehensive approach with a variety of assessments including anthropometry, indirect calorimetry, rigorous nutrient intake inventories, and body composition analysis to determine whether nutrition and growth are optimized for the individual patient.7 Dual x-ray absorptiometry20 and muscle volume magnetic resonance imaging21,22 are proposed as biomarkers suitable for clinical trial assessments of growth.
References
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