Non-Muscle Related Effects of SMA

09 April 2019

This latest article comes from our Clinical Care Research Correspondent, Dr Alex Murphy:


A recent article by Lipnick and colleagues used a novel way to look at some of the non-muscle related effects of SMA. Lipnick and colleagues looked at health insurance claims made by individuals in the United States (US) with SMA, and compared these to claims made by people without SMA1. This article summarises their findings and discusses what they may mean.

Main text

Arguably the most evident symptoms of SMA are caused by muscle weakness, and almost all descriptions of SMA focus on the effects on muscle and development. In medical papers SMA is often referred to as a ‘multi system disease’, meaning it affects several different body organs in different ways. Experiments using animals have shown that there are effects on organs outside of the nerves and muscle2-4. This is thought to be due to the role of SMN in other organs, which is not completely understood. In people, these effects are much less pronounced than those found in animals, but have been recently acknowledged by the recent standards of care review articles with the inclusion of a section on ‘other organ systems’5.

Lipnick and colleagues looked at insurance claims in the US using an insurance database. They looked at the medical records of 1,038 individuals with SMA, and compared this to 39,214,424 controls1. They split the SMA group into approximate SMA Types based on the age at diagnosis. The study found that the groups reported, and may have received treatment for, a number of health conditions previously thought to be unrelated to SMA. In SMA Types 1 and 2 there was an increased risk of problems, such as an issue with an important valve in the heart, difficulties in swallowing, and congenital (since before birth) problems with how the head and neck are formed. In the group representing SMA Type 3, they found increased risk of heart problems by way of holes between the two sides of the heart (septal defects), problems with the development of feet, and development of scoliosis. In the final group (taken to represent SMA Type 4), there was an increased risk of altered sensation, problems with blood vessels, constipation, and males were at risk of reduced fertility. 

A particular strength of the study was the fact that the authors looked at individuals before they became weaker or were diagnosed with SMA, to see which problems were reported. They discuss the fact that most studies concentrate on how individuals are after they have been diagnosed with SMA. The most pressing concern for the family is often due to the weakness of muscles of movement. Other medical needs such as constipation may be less pressing to investigate or treat, but are important to bear in mind.

Lipnick and colleagues point out that the majority of these non-muscle related problems they have found to be more frequent in individuals with SMA have been seen in mice with SMA, but often these effects are far more pronounced in mice than seen in humans with the condition1. The other main suggestion of the paper is that some of these diagnoses may be used in the future to suggest a diagnosis of SMA, as some of these symptoms or diagnoses predate muscle weakness. This suggestion is an interesting one; however currently a number of these symptoms are not considered to be part of what individuals with SMA would necessarily be expected to experience. Several of the conditions which are reported by the study are mild forms of the condition and wouldn’t necessarily prompt a health professional to think of SMA, rather than thinking that the condition was an isolated problem. For example, although this study suggested that those with SMA Types 1 and 2 were seen to have an increased risk of holes between the heart, there are far more individuals who have this problem but do not have SMA than those who have both. This condition is therefore of limited usefulness in assisting in diagnosis without muscular weakness. The findings of the conditions affecting the group representing SMA Type 4 may be more useful to aid diagnosis, as muscular symptoms may be mild, so there is often a much longer time to diagnosis compared with other groups. It is also important to say that not all individuals with SMA will experience these reported problems and are merely at an increased risk of them; this fact again reduces the usefulness of this studies’ findings to aid in diagnosis.


This study is one of the first to look at the non-muscle related problems caused by SMA, and to investigate how individuals may have co-existing health problems prior to onset of muscular weakness. The study does suggest that individuals with SMA have increased risk of several conditions; a fact which can be borne in mind by health professionals when reviewing individuals. Health professionals can then ask targeted questions, potentially finding previously undiagnosed problems related to SMA. The suggestion that the increased risk of certain conditions in those with SMA could be used as a way to assist diagnosis is perhaps less likely. There are currently newborn screening programs6being set up in several countries, which look for SMA in all babies. This is likely to reduce time to diagnosis far more than looking for SMA in patients with the conditions suggested within this paper.


  1. Lipnick SL, Agniel DM, Aggarwal R, Makhortova NR, Finlayson SG, et al. (2019) Systemic nature of spinalmuscular atrophy revealed by studying insurance claims. PLOS ONE 14(3): e0213680.
  2. Heier CR, Satta R, Lutz C, DiDonato CJ. Arrhythmia and cardiac defects are a feature of spinal muscular atrophymodel mice. Hum Mol Genet. 2010 Oct 15;19(20):3906-18. doi: 10.1093/hmg/ddq330.
  3. Shababi M, Habibi J, Yang HT, Vale SM, Sewell WA, Lorson CL. Cardiac defects contribute to the pathology of spinalmuscular atrophy models. Hum Mol Genet. 2010 15; 19 (20):4059-71. doi: 10.1093/hmg/ddq329.
  4. Thomson AK, Somers E, Powis RA, Shorrock HK, Murphy K, Swoboda KJ, Gillingwater TH, Parson SH. Survival of motor neurone protein is required for normal postnatal development of the spleen. J Anat. 2017 Feb;230(2):337-346. doi: 10.1111/joa.12546. Epub 2016 Oct 11.
  5. Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth M, Graham R, Kirschner F, et al. (2018) Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics, Neuromuscular Disorders, 28 (3): 197-207.
  6. Ke Q, Zhao ZY, Mendell JR, Baker M, Wiley V, Kwon JM, Alfano LN, Connolly AM, Jay C, Polari H, Ciafaloni E, Qi M, Griggs RC, Gatheridge MA. (2019) Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophyWorld J Pediatr. doi: 10.1007/s12519-019-00242-6.