WMS 2020 | Overview
Diet, Motor Activity & Daily Activity Limitations in Individuals with SELENON (SEPN1) - Related Myopathy
J.M. Prystupa1, R. Alvarez2, C. A. Genetti1, E. Weller3, S. Liu4, E.C. Troiano1, B. Moghadaszadeh1 & A.H. Beggs1
1Boston Children's Hospital (BCH), Genetics & Genomics, Boston, USA, 2Cure CMD, Lakewood, USA, 3BCH, Hematology Oncology, Biostatistics, ICCTR, Boston, USA, 4BCH, Biostatistics, ICCTR, Boston, USA
Poster
- See below poster for further details.
Abstract
- The abstract was published in the Neuromuscular Disorders October 2020, Supplement 1 (Volume 30) free issue. A link to the specific abstract can be found here.
Introduction
- Mutations in the SELENON (SEPN1) gene result in a group of rare congenital myopathies called SELENON-related myopathies (SELENON-RM)1-5
- SELENON-RM affected individuals typically present early in life with hypotonia and axial weakness, with evolving spinal rigidity, scoliosis, decreased stamina, low body mass, & respiratory insufficiency which in turn can affect an individual's stamina & ability to walk, run, climb stairs, & rise from floor or seated position1,3-7
- The severity of these symptoms varies widely between patients1,3-5 including those with identical mutations6
- An online patient reported outcomes survey was developed to evaluate whether diet can help explain some of this variation
Methods
- 29 participants (21 males, 8 females) with genetically-confirmed SELENON-RM completed a modified version of the EPIC-Food Frequency Questionnaire (EPIC-FFQ)
- Average daily intakes (ADI) were calculated using the FFQ EPIC Tool for Analysis (FETA) software8
- Participants were then asked 24 activity-related questions
(Answer range: 6 = ‘Very Easy’ to 1 = ‘Not Able’ to complete & 0 = ‘Unknown’) - Statistics (correlation, regression) were performed using Microsoft Excel9 & SAS 9.410
Results & Discussion
- All participants answered questions about completing 21 daily activities (DAS)
- 23 participants (79.3%; 18 men, 5 women) answered an additional 3 questions about walking ability (WLS) over short (100ft; flat/inclined) & long (660ft) distances
- See the supplementary information section for details regarding DAS & WLS scoring
- Table 1 contains the descriptive statistics of the categories of interest for the 29 survey participants
Table 1. Summary statistics (DAS = Daily Activity Score, WLS = Walking Scores, ADI = Average Daily Intake). Additional summary statistics for individual daily tasks are provided in Supplementary Tables 1 & 2.
Category |
Median (Range) All (n=29) |
Median (Range) Females (n=8) |
Median (Range) Males (n=21) |
p-value |
---|---|---|---|---|
Age | 23.0 (7 - 56) | 30.5 (7 - 56) | 15.0 (8 - 56) | 0.3139 |
DAS | 74 (25 -105) | 61 (25 - 92) | 81 (26 - 105) | 0.0251 |
WLS | 16 (3 - 18) | 10 (3 - 15) | 17 (7 - 18) | 0.0106 |
ADI - Energy (kcal) | 1334 (654 - 4378) | 1537 (654 - 2527) | 1334 (772 - 4378) | 0.9999 |
ADI - Protein (g) | 70 (26 -133) | 61 (26 - 118) | 73 (42 - 133) | 0.1611 |
ADI - Fat (g) | 64 (27 - 255) | 67 (30 - 163) | 63 (27 - 255) | 0.8466 |
ADI - Carbohydrate (g) | 134 (73 -414) | 140 (75 - 227) | 132 (73 - 414) | 0.6466 |
ADI - Sugars (g) | 61 (19 - 209) | 86 (19 - 131) | 61 (20 - 209) | 0.6815 |
- Males had significantly higher activity scores (DAS & WLS) compared to females
- This is despite consuming a similar amount of total calories, macronutrients & sugars
- Biological differences between genders may help explain some of these observed differences
- Men have increased muscle fiber size & strength compared to women11
- When fat-free mass is considered, women have a higher caloric cost for walking & running compared to men12
- Activity scores were negatively correlated with age (DAS = -0.6333, p = 0.0012; WLS = -0.6640, p = <0.0001 using Spearman Correlation)
- Age & gender is associated with activity scores in a multivariable model (Table 2)
- Age is negatively associated with activity scores
- Males have higher activity scores compared to females
- This is in contrast with previously published data in SELENON-KO animal models, which notes males “having a comparable or more marked phenotype”1 and illustrates that observations in the animal models may not reflect the SELENON-RM human phenotype completely3
Table 2. Multivariable model analysis results for WLS and DAS.
Variable |
WLS β (95%) |
WLS p-value |
DAS β (95%) |
DAS p-value |
---|---|---|---|---|
Age (1 y increase) | -0.2 (-0.2 , -0.1) | <0.0001 | -0.8 (-1.2 , -0.5) | <0.0001 |
Gender (M v F) | 5.5 (3.3 , 7.7) | <0.0001 | 15.0 (2.7 , 27.2) | 0.0168 |
Conclusions & Future Research
- The findings from our research here suggests that both age and gender are significant for influencing perceived activity scores in SELENON-RM affected individuals
- Sample size must be increased before dietary influences can be adequately assessed
- Nevertheless, total calories, macronutrients or sugar intakes do not appear to have any influence on perceived activity scores
- Future research will include expansion of the cohort & further analysis of the survey modules, including investigating associations between specific nutrient intakes & perceived daily activity, walking, & running scores for both males & females, along with age & body mass index & pulmonary information, which could provide additional insight on the variation of symptom severity observed in SELENON-RM affected individuals
Acknowledgements
- We would like to thank the many SELENON-RM affected individuals who took the time to complete the survey. Funding for this project was provided by the Lee & Penny Anderson Family Foundation and utilized the resources of Cure CMD
References
- Filipe, A., A. Chernorudskiy, S. Arbogast, E. Varone, R-N. Villar-Quiles, D. Pozzer, M. Moulin, S. Fumagalli, E. Cabet, S. Dudhal, M-G. De Simoni, R. Denis, N. Vadrot, C. Dill, M. Giovarelli, L. Szweda, C. De Palma, P. Pinton, C. Giorgi, C. Viscomi, E. Clementi, S. Missiroli, S. Boncompagni, E. Zito, and A. Ferreiro. 2020. Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy, Cell Death Differ. doi: 10.1038/s41418-020-0587-z.
- Moghadaszadeh, B., B. E. Rider, M. W. Lawlor, M. K. Childers, R. W. Grange, K. Gupta, S. S. Boukedes, C. A. Owen, and A. H. Beggs. 2013. Selenoprotein N Deficiency in Mice Is Associated with Abnormal Lung Development. FASEB J. 27(4): 1585-99.
- Rederstorff, M., P. Castets, S. Arbogast, J. Lainé, S. Vassilopoulos, M. Beuvin, O. Dubourg, A. Vignaud, A. Ferry, A. Krol, V. Allamand, P. Guicheney, A. Ferreiro, and A. Lescure. 2011. Increased Muscle Stress-Sensitivity Induced by Selenoprotein N Inactivation in Mouse: A Mammalian Model for SEPN1-Related Myopathy, PLOS ONE. 6: e23094.
- Scoto, M., S. Cirak, R. Mein, L. Feng, A. Y. Manzur, S. Robb, A. M. Childs, R. M. Quinlivan, H. Roper, D. H. Jones, C. Longman, G. Chow, M. Pane, M. Main, M. G. Hanna, K. Bushby, C. Sewry, S. Abbs, E. Mercuri & F. Muntoni. 2011. SEPN1-Related Myopathies: Clinical Course in a Large Cohort of Patients. Neurology. 76(24): 2073-8.
- Schara, U., W. Kress, C.G. Bönnemann, N. Breitbach-Faller, C.G. Korenke, G. Schreiber, M. Stoetter, A. Ferreiro, & M. von der Hagen. 2008. The Phenotype and Long-Term Follow-up in 11 Patients with Juvenile Selenoprotein N1-Related Myopathy. Eur J Paediatr Neurol. 12(3): 224-30.
- Clarke, N. F., W. Kidson, S. Quijano-Roy, B. Estournet, A. Ferreiro, P. Guicheney, J.I Manson, A.J. Kornberg, L.K. Shield & K.N. North. 2006. SEPN1: Associated with Congenital Fiber-Type Disproportion and Insulin Resistance. Ann Neurol. 59(3): 546-52.
- Ferreiro, A., S. Quijano-Roy, C. Pichereau, B. Moghadaszadeh, N. Goemans, C. Bonnemann, H. Jungbluth, V. Straub, M. Villanova, J. P. Leroy, N. B. Romero, J. J. Martin, F. Muntoni, T. Voit, B. Estournet, P. Richard, M. Fardeau, and P. Guicheney. 2002. Mutations of the Selenoprotein N Gene, Which Is Implicated in Rigid Spine Muscular Dystrophy, Cause the Classical Phenotype of Multiminicore Disease: Reassessing the Nosology of Early-Onset Myopathies. Am J Hum Genet. 71(4): 739-49.
- Mulligan A, Luben R, Bhaniani A, Parry-Smith D, O’Connor L, Khawaja A, Forouhi NG, Khaw KT. 2014. A new tool for converting food frequency questionnaire data into nutrient and food group values: FETA research methods and availability. BMJ Open. 4(3):e004503.
- Microsoft Corporation. 2018. Microsoft Excel. Available at: https://office.microsoft.com/excel.
- SAS Institute. 2014.SAS: SAS 9.4. Cary, NC.
- Miller, A. E., J. D. MacDougall, M. A. Tarnopolsky, and D. G. Sale.1993. Gender Differences in Strength and Muscle Fiber Characteristics. Eur J Appl Physiol Occup Physiol. 66(3): 254-62.
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Supplemental Material
Activity Information
- Each survey respondent was asked 24 activity questions (see Supplementary Table 1 for details)
- Survey respondents then chose one of the following answers which had a corresponding score (displayed in brackets)
“Very Easy” (6)
“Moderately Easy” (5)
“Not Easy or Hard” (4)
“Moderately Difficult” (3)
“Very Difficult” (2)
“Not Able” (1)
“Unknown” (0)
- Daily Activity Scores (DAS) were calculated from the sum of the 21 (DA1 – DA21) individual daily activity questions (for a maximum score of 126)
- Walking Scores (WLS) were calculated from the sum of the 3 (WL1-WL3) individual walking questions (for a maximum score of 18)
- Supplementary Table 2 shows which activities had the highest and lowest median values for the survey respondents
Supplementary Table 1. The summary statistics for the individual activity related questions
Question Number |
Activity |
Median (Range) All |
Median (Range) Females |
Median (Range) Males |
---|---|---|---|---|
DA1 | Unbutton/button a shirt | 6 (3-6) | 6 (3-6) | 6 (3-6) |
DA2 | Pull a T shirt over head | 5 (1-6) | 4 (2-6) | 5 (1-6) |
DA3 | Shampoo hair in a standing position | 5 (1-6) | 4 (1-6) | 5 (1-6) |
DA4 | Put on socks | 5 (1-6) | 3 (1-6) | 5 (1-6) |
DA5 | Put on pants while standing without the use of a chair or wall to help with balance | 2 (1-6) | 1 (1-3) | 2 (1-6) |
DA6 | Open a twist cap bottle | 5 (1-6) | 4.5 (1-6) | 5 (3-6) |
DA7 | Blow up a balloon | 2 (1-5) | 1 (1-5) | 2 (1-5) |
DA8 | Lift a small 2 lb (0.91 kg) weight to an overhead shelf | 4 (1-6) | 2.5 (1-5) | 5 (1-6) |
DA9 | Pick up a tennis ball from the ground from a standing position | 4 (1-6) | 3.5 (1-5) | 5 (1-6) |
DA10 | Sit in a crossed legged position | 5 (1-6) | 4.5 (1-6) | 5 (1-6) |
DA11 | When standing; tuck chin to chest | 3 (1-6) | 2 (1-6) | 4 (1-6) |
DA12 | Balance on one leg only for 10 seconds | 5 (1-6) | 3.5 (1-6) | 5 (1-6) |
DA13 | Ride a bicycle | 3 (1-6) | 2 (1-4) | 3 (1-6) |
DA14 | Perform a squat | 2 (1-6) | 2 (1-4) | 3 (1-6) |
DA15 | Stand from a chair (of average height) | 4 (1-6) | 3 (1-4) | 5 (1-6) |
DA16 | Stand up from floor | 3 (1-6) | 2 (1-3) | 3 (1-6) |
DA17 | When laying on back; tuck chin to chest | 2 (1-6) | 2 (1-6) | 2 (1-6) |
DA18 | When laying on back; roll onto stomach | 4 (1-6) | 3 (1-6) | 5 (1-6) |
DA19 | When laying on stomach; roll onto back | 4 (1-6) | 3.5 (1-6) | 5 (1-6) |
DA20 | Do a sit-up | 1 (1-6) | 1 (1-2) | 1 (1-6) |
DA21 | Do a push up | 1 (1-4) | 1 (1-3) | 1 (1-4) |
WL1 | Walk a short (100 ft; 30.5 m ) distance on a flat surface | 6 (1-6) | 4 (1-6) | 6 (3-6) |
WL2 | Walk a short (100 ft; 30.5 m) distance on an incline | 5 (1-6) | 3 (1-5) | 5 (2-6) |
WL3 | Walk a long (660 ft; 201 m) distance on a flat surface | 5 (1-6) | 3 (1-4) | 6 (2-6) |
Supplementary Table 2. The individual activities listed by their median value
Median Value |
All |
Females |
Males |
---|---|---|---|
6 “Very Easy” |
• Unbutton/button a shirt • Walk a short (100 ft; 30.5 m) distance on a flat surface |
• Unbutton/button a shirt | • Unbutton/button a shirt • Walk a long (660 ft; 201 m) distance on a flat surface • Walk a short (100 ft; 30.5 m) distance on a flat surface |
5 “Moderately Easy” |
• Balance on one leg only for 10 seconds • Open a twist cap bottle • Pull a T shirt over head • Put on socks • Shampoo hair in a standing position • Sit in a crossed legged position • Walk a long (660 ft; 201 m) distance on a flat surface • Walk a short (100 ft; 30.5 m) distance on an incline |
• Balance on one leg only for 10 seconds • Lift a small 2 lb (0.91 kg) weight to an overhead shelf • Open a twist cap bottle • Pick up a tennis ball from the ground from a standing position • Pull a T shirt over head • Put on socks • Shampoo hair in a standing position • Sit in a crossed legged position • Stand from a chair (of average height) • When laying on back; roll onto stomach • Walk a short (100 ft; 30.5 m) distance on an incline • When laying on stomach; roll onto back |
|
4.5 | • Open a twist cap bottle • Sit in a crossed legged position |
||
4 “Not Easy |
• Lift a small 2 lb (0.91 kg) weight to an overhead shelf • Pick up a tennis ball from the ground from a standing position • Stand from a chair (of average height) • When laying on back; roll onto stomach • When laying on stomach; roll onto back |
• Pull a T shirt over head • Shampoo hair in a standing position • Walk a short (100 ft; 30.5 m) distance on a flat surface |
• When standing; tuck chin to chest |
3.5 | • Balance on one leg only for 10 seconds • Pick up a tennis ball from the ground from a standing position • When laying on stomach; roll onto back |
||
3 “Moderately Difficult” |
• Ride a bicycle • Stand up from floor • When standing; tuck chin to chest |
• Put on socks • Stand from a chair (of average height) • Walk a long (660 ft; 201 m) distance on a flat surface • When laying on back; roll onto stomach |
• Perform a squat • Ride a bicycle • Stand up from floor |
2.5 | • Lift a small 2 lb (0.91 kg) weight to an overhead shelf | ||
2 “Very Difficult” |
• Blow up a balloon • Perform a squat • Put on pants while standing without the use of a chair or wall to help with balance • When laying on back; tuck chin to chest |
• Perform a squat • Ride a bicycle • Stand up from floor • When laying on back; tuck chin to chest • When standing; tuck chin to chest |
• Blow up a balloon • Put on pants while standing without the use of a chair or wall to help with balance • When laying on back; tuck chin to chest |
1 “Not Able” |
• Do a push up • Do a sit-up |
• Blow up a balloon • Do a push up • Do a sit-up • Put on pants while standing without the use of a chair or wall to help with balance |
• Do a sit-up • Do a push up |
This page was last updated October 20, 2020.