Growth pattern trajectories in boys with Duchenne muscular dystrophy.
Deflazacort
Duchenne muscular dystrophy
Glucocorticoids
Growth
Isoforms
Prednisolone
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
24 01 2022
24 01 2022
Historique:
received:
04
10
2021
accepted:
19
12
2021
entrez:
25
1
2022
pubmed:
26
1
2022
medline:
12
3
2022
Statut:
epublish
Résumé
The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD). We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.
Sections du résumé
OBJECTIVES
The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD).
BACKGROUND
We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90).
RESULTS
The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation.
CONCLUSION
These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.
Identifiants
pubmed: 35073949
doi: 10.1186/s13023-021-02158-9
pii: 10.1186/s13023-021-02158-9
pmc: PMC8785507
doi:
Substances chimiques
Dystrophin
0
Glucocorticoids
0
Prednisolone
9PHQ9Y1OLM
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20Investigateurs
Gautam Ambegaonkar
(G)
Zoya Alhaswani
(Z)
Alex Baxter
(A)
Anne-Marie Childs
(AM)
Gabby Chow
(G)
Christian De Goede
(C)
Miguel Fernandez
(M)
Frances Gibbon
(F)
Vasantha Gowda
(V)
Michela Guglieri
(M)
Tony Hart
(T)
Gemunu Hewawitharana
(G)
Iain Horrocks
(I)
Imelda Hughes
(I)
Marjorie Illingworth
(M)
Deepa Krishnakumar
(D)
Anirban Majumdar
(A)
Chiara Marini-Bettolo
(C)
Min Ong
(M)
Deepak Parasuraman
(D)
Sithara Ramdas
(S)
Laurent Servais
(L)
Kate Skone
(K)
Stefan Spinty
(S)
Elma Stephens
(E)
Volker Straub
(V)
Sandya Tirupathi
(S)
Neil Thomas
(N)
Tracey Willis
(T)
Cathy White
(C)
Jarod Wong
(J)
Elizabeth Wraige
(E)
Kayal Vijayakumar
(K)
Karen Naismith
(K)
Informations de copyright
© 2022. The Author(s).
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