Neuromuscular Disorders最新文献

{"title":"229P Home mechanical ventilation in paediatric neuromuscular disorders in a resource limited setting","authors":"R. Ramesh Babu , I. Kinimi , S. Shinde , N. Mohan Rao , A. Sahoo , M. Maganthi , A. Agnes Mathew","doi":"10.1016/j.nmd.2024.07.080","DOIUrl":"10.1016/j.nmd.2024.07.080","url":null,"abstract":"<div><div>Neuromuscular disorders (NMD) have seen a revolution in the availability of novel disease-modifying therapies (DMT) in the last few years. Yet affected individuals often gain suboptimal improvement despite these, due to the paucity of robust allied supportive specialities such as sleep medicine. Sleep Disordered Breathing (SDB) is fairly common in NMD and is the leading cause of death in them. Hence, non-invasive ventilation (NIV) is a crucial part of SDB management. This is often challenging where resources are limited. Here we describe the approach of our referral neuromuscular centre in establishing home mechanical ventilation (HMV) and respiratory care including cough assist. Clinical details of children with neuromuscular diseases attending our centre between January 2018 and August 2022 with SDB were collected by retrospective data review. Level 1 polysomnography (PSG) results of those who underwent the test were retrieved and analysed. 296 children (male: 67.2%, female: 22.8%) with NMD were thus included. The majority of our cohort had spinal muscular atrophy (SMA,165/296), followed by Duchenne muscular dystrophy (DMD, 67/296) and the remaining had other NMD (64/296). 164/296 (55.4%) subjects underwent a PSG. The median Apnoea Hypopnea Index (AHI) was 8.0 (0.3 - 78) per hour of total sleep time. Interestingly, 59.14% of our cohort had moderate to severe OSA. PSG could not be carried out for all individuals with clinical symptoms of SDB due to economic constraints, lack of resources and availability in carrying out PSG in children at a tertiary care unit with its attendant waiting times. Hence we initiated HMV in all subjects with NMD either when they had clinically overt symptoms of SDB or when the PSG supported it or both. HMV was initiated in 243/296 (82.1%) of the subjects included in our cohort. 14 of these individuals underwent a tracheostomy, 32 used cough assist, 22 were on nasogastric tube feeds and 20 underwent gastrostomy with fundoplication. In the subset with SMA: 69/165 (41.87%) children had received one of the DMTs like gene therapy (32/69) or Risdiplam (17/69) or Spinraza (20/69). Initiation of HMV reduced hospital admissions and improved quality of life. 15 children succumbed due to respiratory failure. The use of HMV and cough assist is well established in resource-equipped settings, but is extremely challenging in resource-limited ones, where affected individuals often receive DMT, due to various charitable initiatives without the benefit of adequate respiratory support. But even with these challenges such as long waiting times for PSG, the financial and logistical challenges including those for BiPAP (Bilevel Positive Airway pressure) as well as the cough assistive devices, it is still possible to ensure that subjects have access to them to gain meaningful outcomes from DMTs. In the long run, early initiation reduces the economic burden, both in terms of morbidity and mortality. A low threshold for initiation o","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.71"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"03INV Idiopathic inflammatory myopathies: current state of the field, new insights and treatment","authors":"J. Vencovský,&nbsp;H. Mann","doi":"10.1016/j.nmd.2024.07.014","DOIUrl":"10.1016/j.nmd.2024.07.014","url":null,"abstract":"<div><div>The idiopathic inflammatory myopathies are a heterogeneous group of acquired diseases comprising dermatomyositis (DM), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis (IBM) and myositis occurring in overlap syndromes with other autoimmune systemic diseases. Drug-induced myositis is increasingly seen in association with treatment with statins or checkpoint inhibitors. International collaboration projects in the last decade resulted in better understanding of the genetic predisposition and etiopathogenetic pathways leading to disease initiation and progression, in development of the new disease classification and treatment response criteria, and in a number of large-scale clinical trials with several biologic or targeted synthetic drugs. The new recommendations for cancer screening in myositis are an important clinical aid. In addition to more refined characterisation of the association with HLA molecules, the relationship of IIM to other non-HLA genes or to low gene copy number of complement has been demonstrated. Further evidence is emerging for an important role of autoantibodies, not only in relation to clinical manifestations and prognosis, but also in terms of a possible pathogenic effect in the disease. Attention is now also being paid to organ involvement in myositis, particularly the lungs, as new therapeutic options for interstitial lung disease became available. Several new clinical trials with biologics have generally failed to demonstrate sufficient efficacy in the treatment of IIM, although there are signals of a possible benefit in some subtypes of IIM. A landmark clinical trial with intravenous immunoglobulins has provided evidence of significant efficacy in patients with DM leading to a new regulatory approval in many years. A number of other clinical trials are currently underway in various subtypes of IIM, including notoriously resistant IBM, with drugs that have very intriguing mechanisms of action and some have already been shown to be effective in similar immune-mediated diseases. Results will be known in the coming months/years.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.5"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"221P Initial data from the achieve trial of DYNE-101 in adults with myotonic dystrophy type 1 (DM1)","authors":"D. Wolf ,&nbsp;J. Lilleker ,&nbsp;G. Bassez ,&nbsp;J. Diaz-Manera ,&nbsp;J. Kools ,&nbsp;M. Pane ,&nbsp;R. Roxburgh ,&nbsp;B. Schoser ,&nbsp;C. Turner ,&nbsp;C. Mix ,&nbsp;S. Ray ,&nbsp;B. Han ,&nbsp;W. Farwell ,&nbsp;V. Sansone","doi":"10.1016/j.nmd.2024.07.072","DOIUrl":"10.1016/j.nmd.2024.07.072","url":null,"abstract":"<div><div>DM1 is a spliceopathy caused by expansion of CUG repeats in the DMPK RNA that leads to multisystem clinical manifestations. DYNE-101, an investigational therapeutic for treatment of DM1, consists of a TfR1-binding Fab conjugated to an ASO designed against mutant nuclear DMPK RNA to correct splicing. The safety and efficacy of DYNE-101 in adults (18-49 years old) are being investigated in the Phase1/2 ACHIEVE trial (NCT05481879). For this analysis, 16 participants had efficacy data through 6 months (6M) of follow-up in the 1.8 mg/kg (approximate ASO) dose cohort and 16 participants had biopsy data through 3M of follow-up in the 3.4 mg/kg dose cohort of the MAD portion of ACHIEVE. Participants were randomized to receive DYNE-101 (n=6) or placebo (n=4) Q4W, or two doses of DYNE-101 followed by placebo for the remainder of the MAD period (n=6). Safety and tolerability are based on 45 participants enrolled in ACHIEVE as of the data cut-off date. At 3M, 1.8 and 3.4 mg/kg DYNE-101 showed mean 10.0 ng/g and 21.5 ng/g ASO concentration, mean 25% and 40% DMPK knockdown, and mean 13% and 19% splicing correction from baseline, respectively. At 6M, 1.8 mg/kg DYNE-101 showed mean 16% DMPK knockdown, +7% CASI change from baseline, 3.8-second improvement in myotonia, and improvement in MDHI, a patient-reported outcome. 3/5 evaluable participants had splicing correction at 3M, persisting through 6M. In the 3.4 mg/kg cohort, 5/5 evaluable participants had splicing correction at 3M. DYNE-101 had a favorable safety profile as of the data cut-off date, with mostly mild or moderate TEAEs and no clinically meaningful changes in kidney and liver parameters or treatment-emergent anemia. The initial data with DYNE-101 demonstrated dose-dependent ASO delivery, DMPK knockdown, and splicing correction with durable effect. Improvement in myotonia was also observed at the lowest dose tested. The data support the continued development of DYNE-101 for the treatment of DM1.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.63"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"223P Mental health support for children and young people with Duchenne muscular dystrophy – who, when and how across the UK","authors":"C. Geagan ,&nbsp;A. Sandhu ,&nbsp;L. Bouquillon ,&nbsp;R. Conn ,&nbsp;D. Bindman ,&nbsp;J. Pattni ,&nbsp;C. Turner ,&nbsp;R. McDonald ,&nbsp;J. Alex ,&nbsp;S. Rodney ,&nbsp;R. Quinlivan ,&nbsp;M. Guglieri ,&nbsp;V. Straub","doi":"10.1016/j.nmd.2024.07.074","DOIUrl":"10.1016/j.nmd.2024.07.074","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations in the gene that codes for dystrophin. Patients experience a gradual loss of muscle starting in childhood that usually leads to death in the late 20s. Whilst the physical impact is well documented, the psychological and neuropsychological impact of this condition on children and young people (CYP) with DMD and their families has been largely overlooked and is poorly understood. The objective of the survey was to acquire qualitative and quantitative information about approaches to and provision for mental health (MH) needs in CYP with DMD across the UK. To identify areas of good practice as well as gaps in service provision and variation and inequity in access to services which will inform approaches to service improvement. Professionals across the NorthStar network (consortium of all the UK neuromuscular paediatric centres) and parents/caregivers will be recruited using separate online surveys. Questions have been designed by the project team and cover a range of similar themes regarding psychosocial support allowing comparison across the groups. CYP with DMD and their parents/caregivers will be invited to separate focus groups or interviews to discuss their views on support for mental health in DMD. Results are in progress. We hypothesise that MH support for CYP and their carers will be identified as an essential component of care that should be offered in the neuromuscular clinic, as part of a broader interdisciplinary integrated approach. Understanding viewpoints from different stakeholders is essential in the early stages of this project to help guide future research ideas and clinical practice. Further engagement with CYP and parents/carers regionally and nationally is crucial to service development. This project will be part of the wider DMD Care UK project which aims to provide consensus and an evidence base for the highest standard of care for all aspects of DMD. This is leading to UK-wide care recommendations, referral pathways, prescription guidance and clinical practice guidelines. Our work will embed psychosocial care within multidisciplinary teams treating DMD throughout the UK.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.65"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"04INV Acquired muscle disorders - a paediatric perspective","authors":"S. Ramdas","doi":"10.1016/j.nmd.2024.07.015","DOIUrl":"10.1016/j.nmd.2024.07.015","url":null,"abstract":"<div><div>Acquired muscle disorders comprise of a heterogenous group of treatable infectious or inflammatory disorders. Outside the benign self-limiting viral myositis, the most common acquired muscle disorders are Immune mediated myopathies (IIMs) which include juvenile dermatomyositis, juvenile polymyositis and immune-mediated necrotising myopathy. IIMs are rare in paediatric cohorts with an annual incidence of 1.6- 4 cases/million children compared to adult incidence of 0.2-2/100,000 person years, leading to diagnostic delay including misdiagnosis as genetic or para-infectious muscle disorders and consequently morbidity and mortality due to treatment delay. The talk will cover the pathophysiology mechanisms, clinical presentations, current and emerging treatment strategies in management of paediatric acquired muscle disorders focusing particularly on the nuances of the issues which are pertinent to children and young people compared to adults.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.6"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"361P Development of a next-generation multiplex ddPCR assay for measurement of in-frame dystrophin mRNA in people with DMD treated with BMN 351","authors":"S. Tamura,&nbsp;I. Sidhu,&nbsp;J. Ilagan,&nbsp;A. Yu,&nbsp;A. Byer,&nbsp;S. Kamath,&nbsp;L. Staskus,&nbsp;C. Russell,&nbsp;A. Melton,&nbsp;K. Larimore","doi":"10.1016/j.nmd.2024.07.098","DOIUrl":"10.1016/j.nmd.2024.07.098","url":null,"abstract":"<div><div>BMN 351, a next-generation antisense oligonucleotide (ASO), is being developed for the treatment of people with Duchenne muscular dystrophy (DMD) who have mutations amenable to exon 51 skipping. Out-of-frame dystrophin mRNA transcripts are converted by exon 51 skipping to in-frame, near-full–length, functional dystrophin transcripts. In-frame dystrophin mRNA expression is an early pharmacodynamic marker of BMN 351 activity. Current standard methods measure mRNA skipping by calculating the percentage of in-frame (exon skipped) dystrophin transcripts over total dystrophin transcripts. However, the relationship between exon skip percentage and dystrophin protein expression is unclear, as measurement of exon skip percentage does not account for reduced total dystrophin mRNA in DMD muscle. Here, we propose a novel assay strategy that quantifies functional in-frame dystrophin mRNA as a percentage of normal in-frame dystrophin transcripts from control muscle. This enhances the value of dystrophin mRNA measurements and better aligns with and predicts protein expression. Using in silico data mining and experimental verification, we identified both ubiquitously expressed and muscle-specific normalizer transcripts that can be measured in a multiplex ddPCR method with in-frame and total dystrophin mRNA. Ubiquitously expressed normalizers enable reporting of in-frame dystrophin mRNA levels normalized to total cellular content, compensating for varying RNA quantity and quality between samples. Muscle-specific normalizers provide insight into in-frame dystrophin mRNA expression per muscle cell in biopsies that may contain inflammatory infiltrate and adipocyte cells that vary with disease state and across individual biopsies. In this next-generation multiplex approach we propose a strategy to provide a more comprehensive and clinically relevant evaluation of mRNA expression that may be more predictive of functional dystrophin protein levels following ASO treatment for DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.89"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"362P Whole-body MRI reveals common and distinctive muscle involvement in “clinically asymptomatic” female carriers of pathogenic DMD variants","authors":"F. Giliberto ,&nbsp;A. Vigliano ,&nbsp;L. Luce ,&nbsp;J. Pastor Rueda ,&nbsp;H. Chaves ,&nbsp;L. Mesa ,&nbsp;M. Carcione ,&nbsp;C. Mazzanti ,&nbsp;C. Llames Massini ,&nbsp;P. Radic ,&nbsp;C. Cejas","doi":"10.1016/j.nmd.2024.07.099","DOIUrl":"10.1016/j.nmd.2024.07.099","url":null,"abstract":"<div><div>DMD-carriers were traditionally considered asymptomatic given the X-linked recessive inheritance pattern of these diseases. Yet, it has recently been discovered that they exhibit different levels of muscle involvement.</div><div>This study aimed to characterize and compare the muscle structure on MRI of DMD-carriers and a control group. Secondly, we pursue a correlation between levels of muscle involvement and clinical manifestations, creatine kinase (CK) levels, DMD molecular alteration and X-chromosome inactivation (XCI) patterns. We enrolled 30 genetically confirmed DMD female carriers and 30 healthy non-carrier controls, BMI and age matched. All individuals underwent whole-body MRI, where semi-quantitative scales were used to assess muscle edema, trophism and fatty infiltration. Neurological examination, Serum CK measurement, DMD genetic screening, and XCI studies were only performed on the DMD-carriers. Statistically significant differences in muscle involvement were observed between DMD-carriers and the control group. Female carriers exhibited muscle affection in 33% of the 48 muscle groups analyzed, while the control group presented only the 10% affected. Most of the DMD-carriers’ implicated muscles showed mild atrophy and mild to moderate fatty infiltration. The muscles more frequently affected were gastrocnemius, gluteus maximus and soleus. No statistical correlation was found between the levels or pattern of muscle involvement on MRI and the neurological examination, CK values, type of genetic variant and XCI patterns. DMD-carriers exhibit frequent and distinctive muscle involvement patterns on MRI, questioning the conception of “asymptomatic” DMD-Carriers. These results, together with findings in other X-linked disorders, lead to a revision of the concept of asymptomatic carriers of X-linked recessive diseases and raise awareness of the need to develop best practice guidelines for the evaluation and management of these females.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.90"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to the 29th World Muscle Society Congress in Prague, Czechia, 2024","authors":"","doi":"10.1016/j.nmd.2024.08.002","DOIUrl":"10.1016/j.nmd.2024.08.002","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104445"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"147VP Efficacy and safety of Nusinersen in the treatment of spinal muscular atrophy in adolescents and adults","authors":"W. Ningning ,&nbsp;Y. Hu ,&nbsp;L. Yu ,&nbsp;W. Zhu","doi":"10.1016/j.nmd.2024.07.054","DOIUrl":"10.1016/j.nmd.2024.07.054","url":null,"abstract":"&lt;div&gt;&lt;div&gt;We aimed to explore the efficacy and safety of Nusinersen treatment in terms of motor function and electrophysiological indicators in Chinese adolescents and adults with SMA. The study included adolescent and adult SMA patients diagnosed at Huashan Hospital affiliated with Fudan University, The First Affiliated Hospital of Soochow University, and The First Affiliated Hospital of Anhui Medical University from October 2022 to December 2023, who received at least 4 doses of Nusinersen. Assessments of motor scales and pulmonary function, including the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walk Test (6MWT), and forced vital capacity (FVC%), were conducted the day before the 1st, 4th, 5th, and 6th treatments (V1, V4, V5, V6). Electrophysiological indicators, including compound muscle action potential (CMAP) and motor unit number index (MUNIX) for upper and lower limb nerves, were also collected to compare improvements in these metrics before and after treatment. A total of 54 patients were included in the study and divided into two groups: those able to walk independently (ambulatory group) and those unable to walk independently but able to sit independently (non-ambulatory group). The average age of the patients was 27.03 years (range 13-53 years), with 64.81% being male. Type II accounted for 16.67% (9/54), and Type III for 79.63% (43/54). Changes in HFMSE scores were statistically significant in both the non-ambulatory and ambulatory subgroups. In the ambulatory subgroup, HFMSE scores improved from baseline to V4 (mean +2.3 points, P=0.004), V5 (+3.0 points, P=0.004), and V6 (+4.2 points, P=0.005), with the ambulatory group showing more pronounced improvements compared to the non-ambulatory group. There was no statistically significant change in the average RULM score from baseline to V4, V5, and V6, but a positive trend was observed, with more marked improvements in the non-ambulatory group. The 6MWT showed significant improvement, with 33.33% (5/15), 66.67% (9/15), and 80.00% (12/15) of patients demonstrating clinically meaningful improvements at V4, V5, and V6, respectively. The CMAP and MUNIX values of upper and lower limb muscles showed a positive correlation with SMN2 copy numbers, motor function status, and baseline motor function scores. After treatment, the most significant increases were observed in the abductor digiti minimi (+0.92mV, P&lt;0.001), trapezius (+0.86mV, P&lt;0.001), and abductor pollicis brevis (+0.81mV, P&lt;0.001) muscles, and lower limb muscles (tibialis anterior +0.44mV, P=0.017). The MUNIX results were similar to CMAP values, with upper limb improvements being superior to lower limbs. A CMAP value of the trapezius muscle ≥ 1.76 mV suggested that patients were more likely to respond to treatment by day 300 (sensitivity 84.6%, specificity 85.7%). With the extension of treatment duration, the incidence rate of adverse reactions remained stable, mainly pres","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.45"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"129P Newborn screening for spinal muscular atrophy in Poland – a summary of 3-year experience","authors":"M. Gos ,&nbsp;J. Wasiluk ,&nbsp;A. Landowska ,&nbsp;M. Jurzyk ,&nbsp;W. Wawer ,&nbsp;P. Kubiszyn ,&nbsp;J. Wieczorek ,&nbsp;O. Kordowska ,&nbsp;L. Nosarieva ,&nbsp;K. Durda ,&nbsp;M. Fraczyk ,&nbsp;M. Jedrzejowska ,&nbsp;M. Ołtarzewski","doi":"10.1016/j.nmd.2024.07.036","DOIUrl":"10.1016/j.nmd.2024.07.036","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is a rare disorder that affects about 1/7000-8000 people in Poland.</div><div>The disease can be successfully treated with available targeted drugs such as nusinersen, onasemnogene abeparvovec and risdiplam that are available from public funds for every SMA patient. The newborn screening for SMA has been implemented in March 2022 and since then it was implemented in whole country as a part of National Newborn Screening Programme. Herein, we present our three-year experience with SMA as a routine part of NBS. Newborn screening for SMA as a genetic test is not obligatory and parents have to consent for molecular testing (opt-in). Standard dried blood spots are used for DNA extraction and a PCR-HRM based test (SALSA MC002 SMA Newborn Screen test, MRC-Holland) is used for screening. After the positive result of first-tier test, we perform follow-up testing with MLPA technique (P021 kit, MRC-Holland). During 3 years, over 750 000 newborns were screened and SMA has been confirmed in 101 children that were admitted to regional children neurological clinics. The results of the first-tier test and MLPA verification from blood spot were ready on the 8th day of life (mean: 8.5±3.7; 3 days since registration in the central database). On the day 14th (mean 14.7±5.0; 9 days since registration), the results of the verification test were available. About 70% of diagnosed patients were asymptomatic, others presented mild symptoms of the disease. Three children with 1 SMN2 copy presented with SMA0. The treatment was implemented as soon as possible if patients were carrying from 1 to 3 SMN2 copies (2, 27 and 39 children, respectively). On average, therapy was started at 22nd day of life. The newborn screening for SMA was successfully implemented in Poland and became a part of the routine screening. Our procedure allows for quick identification of SMA patients that would benefit from targeted therapies. Based on the population data, the prevalence of SMA can be estimated at ≈1/7500.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.27"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}