INTRODUCTION: Treatment of children with spinal muscular atrophy (SMA) now includes disease modifying drugs such as nusinersen. Real-world data can provide new insight on the efficacy and safety of nusinersen for treatment of children with SMA. AIM: The aim of our study is to evaluate the effect of treatment of children and young adults with SMA type I, II and III at various stages of the disease after 14 months of treatment with nusinersen. METHODS: In this prospective, two-center (in Slovenia and Czech Republic) study, data from all patients with a genetically confirmed diagnosis of SMA before 19 years of age who were treated with nusinersen were collected before initiation of treatment, and after 6 and 14 months of treatment. Various standardized motor scales and a questionnaire that focused on daily-life activities were used. RESULTS: Form both centers, 61 patients from 2 months to 19 years of age were enrolled in the study. Sixteen had SMA type I (median age 5.2 years); 32 had SMA type II (median age 8.9 years); and 13 had SMA type III (median age 8.6 years). Patients had 2-4 copies of the SMN2 gene. One patient died in the study period and one discontinued treatment. After 14 months of treatment, SMA type I (p = 0.002) and type II (p = 0.002) patients had significantly better outcomes, while type III patients showed a trend towards improvement (p = 0.051) on motor scales. Younger age at the initiation of treatment and a higher number of SMN2 copies is related to a better outcome. Younger children also seem to improve faster compared to older children. No serious side effects were reported. CONCLUSION: The results of our study which included patients of various SMA types and stages of the disease suggest that treatment with nusinersen benefits patients, regardless of SMA type. Earlier age at the initiation of treatment and a higher number of SMN2 copies were related to a better outcome, however even some patients of higher age and/or later stage of the disease benefited from the treatment. Our study also suggests that nusinersen is safe to use, as no major side effects, requiring discontinuation of treatment, were reported. There is an unmet need for novel standardized tests and biomarkers, which could help guide clinician's decisions on the selection of best treatment options and monitor treatment success.

• MeSH
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Oligonucleotides therapeutic use   MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Muscular Atrophy, Spinal drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Slovenia MeSH

Cíl: Popis průběhu a komplikací Duchennovy (DMD) a Beckerovy (BMD) svalové dystrofie v dětském věku. Soubor a metodika: Restrospektivní analýza klinických a laboratorních dat se zaměřením na svalové a mimosvalové komplikace 78 chlapců s dystrofinopatií (65 DMD a 13 BMD) sledovaných v našem nervosvalovém centru v letech 2004–2018. Výsledky: Zatímco chlapci s BMD měli zanedbatelný výskyt sekundárních komplikací, chlapci s DMD byli ohroženi závažnými komplikacemi již od druhé dekády života. Celkem 43 (66 %) chlapců s DMD bylo léčeno kortikoidy. Chlapci léčení kortikoidy v průměru ztratili schopnost chůze o 1,3 roku později než chlapci neléčení (p < 0,001). U 54 % chlapců s DMD starších 12 let byla dia­gnostikována středně těžká restriktivní plicní porucha, nejvýznamnějším rizikovým faktorem byla ztráta schopnosti chůze (p < 0,001). Sníženou ejekční frakci či fibrózu myokardu mělo 45 % chlapců starších 10 let. Chlapci s DMD měli ve 40 % malý vzrůst, jehož výskyt stoupal s věkem (p < 0,0001). Osteoporóza byla dia­gnostikována u 22 % chlapců s DMD, častěji u léčených kortikoidy než u neléčených (p = 0,024). Tranzientní proteinurie v bio­chemickém vyšetření moči byla u 48 % chlapců s DMD. Psychologické odchylky mělo 68 % chlapců s DMD. Závěr: Tato studie vychází z dosud nejrozsáhlejšího souboru dětských pacientů s dystrofinopatií v ČR a zdůrazňuje potřebu multioborového přístupu v péči o ně.

Aim: Description of natural course and variety of complications in Duchenne (DMD) and Becker (BMD) muscular dystrophies in childhood. Patients and methods: Retrospective analysis of clinical and laboratory data with focus on muscular and extramuscular complications in 78 boys with dystrophinopathy (65 with DMD and 13 with BMD) followed up in our neuromuscular centre between 2004 and 2018. Results: The incidence of secondary complications was negligible in boys with BMD. On the other hand, boys with DMD suffered from severe complications from their second decade of age. Overall 43 (66%) of the boys with DMD were treated with glucocorticoids. Glucocorticoid-treated boys lost ability to walk on average 1.3 years later than glucocorticoid-naive boys (P < 0.001). Moderate restrictive lung disease was diagnosed in 54% of boys with DMD older than 12 years of age, and loss of ability to walk was the most significant risk factor (P < 0.001). Decreased ejection fraction or myocardial fibrosis was found in 45% of boys older than 10 years of age. Boys with DMD had short stature in 40%, the incidence of which increased with age (P < 0.0001). Osteoporosis was diagnosed in 22% of boys with DMD, more often in the glucocorticoid-treated group than in glucocorticoid-naive group (P = 0.024). Transient proteinuria was described in 48% of boys with DMD. Psychological aberrations were described in 68% of boys with DMD. Conclusion: This study describes the most extensive cohort of pediatric patients with dystrophinopathy in the Czech Republic and highlights the need of multidisciplinary care.

• MeSH
• Child MeSH
• Muscular Dystrophy, Duchenne * complications   MeSH
• Cardiomyopathies MeSH
• Humans MeSH
• Osteoporosis MeSH
• Proteinuria MeSH
• Respiratory Insufficiency MeSH
• Retrospective Studies MeSH
• Patient Care Team MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3-6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.

• MeSH
• Child MeSH
• Adult MeSH
• Genetic Association Studies * methods   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Muscular Dystrophies, Limb-Girdle diagnosis   epidemiology   genetics   MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Sarcoglycanopathies diagnosis   epidemiology   genetics   MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH