Journal of neuromuscular diseases最新文献

{"title":"Gene Distribution in Pediatric-Onset Inherited Peripheral Neuropathy: A Single Tertiary Center in Thailand.","authors":"Pimchanok Kulsirichawaroj, Yanin Suksangkharn, Da Eun Nam, Theeraphong Pho-Iam, Chanin Limwongse, Ki Wha Chung, Oranee Sanmaneechai, Stephan L Zuchner, Byung-Ok Choi","doi":"10.3233/JND-230174","DOIUrl":"10.3233/JND-230174","url":null,"abstract":"<p><strong>Background: </strong>Inherited peripheral neuropathy presents a diagnostic and therapeutic challenge due to its association with mutations in over 100 genes. This condition leads to long-term disability and poses a substantial healthcare burden on society.</p><p><strong>Objective: </strong>This study aimed to investigate the distribution of genes and establish the genotype-phenotype correlations, focusing on pediatric-onset cases.</p><p><strong>Methods: </strong>Exome sequencing and other analytical techniques were employed to identify pathogenic variants, including duplication analysis of the PMP22 gene. Each patient underwent physical examination and electrophysiological studies. Genotypes were correlated with phenotypic features, such as age at disease onset and ulnar motor nerve conduction velocity.</p><p><strong>Results: </strong>We identified 35 patients with pediatric-onset inherited peripheral neuropathy. Pathogenic or likely pathogenic variants were confirmed in 24 out of 35 (68.6%) patients, with 4 of these variants being novel. A confirmed molecular diagnosis was achieved in 90.9% (10/11) of patients with demyelinating Charcot-Marie-Tooth disease (CMT) and 56.3% (9/16) of patients with axonal CMT. Among patients with infantile-onset CMT (≤2 years), the most common causative genes were MFN2 and NEFL, while GDAP1 and MFN2 were frequent causes among patients with childhood- or adolescent-onset CMT (3-9 years).</p><p><strong>Conclusions: </strong>The MFN2 gene was the most commonly implicated gene, and the axonal type was predominant in this cohort of Thai patients with pediatric-onset inherited peripheral neuropathy.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"191-199"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening.","authors":"Heike Kölbel, Marius Kopka, Laura Modler, Astrid Blaschek, Ulrike Schara-Schmidt, Katharina Vill, Oliver Schwartz, Wolfgang Müller-Felber","doi":"10.3233/JND-230136","DOIUrl":"10.3233/JND-230136","url":null,"abstract":"<p><strong>Objective: </strong>Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown.</p><p><strong>Methods: </strong>40 of 47 eligible SMA patients (23 females/17 males) from 39 families identified through newborn screening between January 2018 and December 2020 underwent developmental testing using Bayley III (BSID) after the 2 years of age. The mean age was 29.25 months (23-42 months). 17 patients had 2, 11 patients had 3 and 12 patients had ≥4 copies of SMN2.</p><p><strong>Results: </strong>cognitive scale: mean 94.55 (SD 24.01); language scale: mean 86.09 (SD 26.41); motor scale: 81.28 (SD 28.07). Overall, the cognitive scales show that 14 children were below average, 20 children were average and 6 children were above average. 10/14 children with below average scores had 2 SMN2 copies. The post-hoc pairwise comparisons showed that the cognition main scale was significantly more sensitive to the number of SMN2 copies than the motor main scale of the BSID (MΔ= 10.27, p = 0.014). There is also evidence that cognition scored higher than the language main scale (MΔ= 7.11, p = 0.090).</p><p><strong>Conclusion: </strong>The impaired cognitive development of SMA children with 2 SMN2 copies, despite early initiation of therapy, underscores the critical role of the SMN protein in the early stages of brain development.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"143-151"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.","authors":"Karlijn Bouman, Frederik M A van den Heuvel, Reinder Evertz, Ewout Boesaard, Jan T Groothuis, Baziel G M van Engelen, Robin Nijveldt, Corrie E Erasmus, Floris E A Udink Ten Cate, Nicol C Voermans","doi":"10.3233/JND-230190","DOIUrl":"10.3233/JND-230190","url":null,"abstract":"<p><strong>Background: </strong>LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking.</p><p><strong>Objective: </strong>The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care.</p><p><strong>Methods: </strong>In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction.</p><p><strong>Results: </strong>21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients.</p><p><strong>Conclusion: </strong>ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"919-934"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Heterogeneity of Nuclear Envelopathy Related Muscular Dystrophies in an Indian Cohort.","authors":"Dipti Baskar, Veeramani Preethish-Kumar, Kiran Polavarapu, Seena Vengalil, Saraswati Nashi, Deepak Menon, Valakunja Harikrishna Ganaraja, Manu Santhappan Girija, Bevinahalli Nanjegowda Nandeesh, Gautham Arunachal, Atchayaram Nalini","doi":"10.3233/JND-230172","DOIUrl":"10.3233/JND-230172","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear envelopathies occur due to structural and/or functional defects in various nuclear envelope proteins such as lamin A/C and lamin related proteins. This study is the first report on the phenotype-genotype patterns of nuclear envelopathy-related muscular dystrophies from India.</p><p><strong>Methods: </strong>In this retrospective study, we have described patients with genetically confirmed muscular dystrophy associated with nuclear envelopathy. Data on clinical, laboratory findings and muscle MRI were collected.</p><p><strong>Results: </strong>Sixteen patients were included with median age at onset of 3 years (range: 1 month - 17 years). Three genes were involved: LMNA (11, 68.75%), EMD (4, 25%) and SYNE1 (1, 6.25%). The 11 patients with LMNA variants were Congenital muscular dystrophy (MDCL)=4, Limb Girdle Muscular Dystrophy (LGMD1B)=4 and Emery-Dreifuss Muscular Dystrophy (EDMD2)=3. On muscle biopsy, one patient from each laminopathy phenotype (n = 3) revealed focal perivascular inflammatory infiltrate. Other notable features were ophthalmoparesis in one and facial weakness in one. None had cardiac involvement. Patients with EDMD1 had both upper (UL) and lower limb (LL) proximo-distal weakness. Cardiac rhythm disturbances such as sick sinus syndrome and atrial arrhythmias were noted in two patients with EDMD1. Only one patient with variant c.654_658dup (EMD) lost ambulation in the 3rd decade, 18 years after disease onset. Two had finger contractures with EMD and SYNE1 variants respectively. All patients with LMNA and SYNE1 variants were ambulant at the time of evaluation. Mean duration of illness (years) was 11.6±13 (MDCL), 3.2±1.0 (EDMD2), 10.4±12.8 (LGMD1B), 11.8±8.4 (EDMD1) and 3 (EDMD4). One patient had a novel SYNE1 mutation (c.22472dupA, exon 123) and presented with UL phenotype and prominent finger and wrist contractures.</p><p><strong>Conclusion: </strong>The salient features included ophthalmoparesis and facial weakness in LMNA, prominent finger contractures in EMD and SYNE1 and upper limb phenotype with the novel pathogenic variant in SYNE1.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"969-979"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.","authors":"Payam Mohassel, Meher Abdullah, Florian S Eichler, Teresa M Dunn","doi":"10.3233/JND-240014","DOIUrl":"10.3233/JND-240014","url":null,"abstract":"<p><p>Motor neuron diseases and peripheral neuropathies are heterogeneous groups of neurodegenerative disorders that manifest with distinct symptoms due to progressive dysfunction or loss of specific neuronal subpopulations during different stages of development. A few monogenic, neurodegenerative diseases associated with primary metabolic disruptions of sphingolipid biosynthesis have been recently discovered. Sphingolipids are a subclass of lipids that form critical building blocks of all cellular and subcellular organelle membranes including the membrane components of the nervous system cells. They are especially abundant within the lipid portion of myelin. In this review, we will focus on our current understanding of disease phenotypes in three monogenic, neuromuscular diseases associated with pathogenic variants in components of serine palmitoyltransferase, the first step in sphingolipid biosynthesis. These include hereditary sensory and autonomic neuropathy type 1 (HSAN1), a sensory predominant peripheral neuropathy, and two neurodegenerative disorders: juvenile amyotrophic lateral sclerosis affecting the upper and lower motor neurons with sparing of sensory neurons, and a complicated form of hereditary spastic paraplegia with selective involvement of the upper motor neurons and more broad CNS neurodegeneration. We will also review our current understanding of disease pathomechanisms, therapeutic approaches, and the unanswered questions to explore in future studies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"735-747"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Cognition, Affective Symptoms, and Apathy in Treatment Adherence with Noninvasive Home Mechanical Ventilation in Myotonic Dystrophy.","authors":"Bettine A H Vosse, Jasmijn de Jong, Leandre A la Fontaine, Corinne G C Horlings, Sander M J van Kuijk, Nicolle A M Cobben, Anne-Fleur Domensino, Caroline van Heugten, Catharina G Faber","doi":"10.3233/JND-240081","DOIUrl":"10.3233/JND-240081","url":null,"abstract":"<p><strong>Background: </strong>Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood.</p><p><strong>Objective: </strong>The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1.</p><p><strong>Methods: </strong>The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days).</p><p><strong>Results: </strong>Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence.</p><p><strong>Conclusions: </strong>This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1123-1130"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.","authors":"Walaa Karazi, Jacqueline Coppers, Daphne Maas, Edith Cup, Bart Bloemen, Nicole Voet, Jan T Groothuis, Tomàs Pinós, Ramon Marti Seves, Ros Quinlivan, Nicoline Løkken, John Vissing, Salman Bhai, Andrew Wakelin, Stacey Reason, Nicol C Voermans","doi":"10.3233/JND-230027","DOIUrl":"10.3233/JND-230027","url":null,"abstract":"<p><strong>Background: </strong>Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance.</p><p><strong>Objective: </strong>This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance.</p><p><strong>Methods: </strong>An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5.</p><p><strong>Results: </strong>One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources.</p><p><strong>Conclusion: </strong>Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"103-116"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Early Treatment of Inherited Neuromuscular Conditions.","authors":"Laurane Mackels, Laurent Servais","doi":"10.3233/JND-230189","DOIUrl":"10.3233/JND-230189","url":null,"abstract":"<p><p>There has been tremendous progress in treatment of neuromuscular diseases over the last 20 years, which has transformed the natural history of these severely debilitating conditions. Although the factors that determine the response to therapy are many and in some instance remain to be fully elucidated, early treatment clearly has a major impact on patient outcomes across a number of inherited neuromuscular conditions. To improve patient care and outcomes, clinicians should be aware of neuromuscular conditions that require prompt treatment initiation. This review describes data that underscore the importance of early treatment of children with inherited neuromuscular conditions with an emphasis on data resulting from newborn screening efforts.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"253-274"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural History of Mandibular Function in Spinal Muscular Atrophy Types 2 and 3.","authors":"H Willemijn van Bruggen, Camiel A Wijngaarde, Faylynn Asselman, Marloes Stam, Nico H J Creugers, Renske I Wadman, W Ludo van der Pol, Stanimira I Kalaykova","doi":"10.3233/JND-240007","DOIUrl":"10.3233/JND-240007","url":null,"abstract":"<p><strong>Background: </strong>Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course.</p><p><strong>Objective: </strong>In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3.</p><p><strong>Methods: </strong>We included 44 patients with SMA types 2 and 3 (mean age was 33.6 (95% CI 28.4;38.9) and re-examined them after on average 4 years. None were treated with SMN-modulating treatments before or during the course of this study. Longitudinal assessments included a questionnaire on mandibular and bulbar function, the Mandibular Function Impairment Questionnaire (MFIQ), and a clinical examination of masticatory performance, maximum voluntary bite force, and mandibular movements including the active maximal mouth opening.</p><p><strong>Results: </strong>We found significant higher MFIQ scores and a significant decrease of all mandibular movements in patients with SMA type 2 (p < 0.001), but not in SMA type 3. Masticatory performance and maximum voluntary bite force did not change significantly. Mean reduction of active maximal mouth opening at follow-up was 3.5 mm in SMA type 2 (95% CI: 2.3; 4.7, p < 0.001). SMA type 2 was an independent predictor for a more severe reduction of the mouth opening (β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)).</p><p><strong>Conclusions: </strong>Bulbar functions such as mandibular mobility and active maximum mouth opening decrease significantly over the course of four years in patients with SMA type 2.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"655-664"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcome of Infantile Onset Pompe Disease Patients Treated with Enzyme Replacement Therapy - Data from a German-Austrian Cohort.","authors":"Charlotte Pfrimmer, Martin Smitka, Nicole Muschol, Ralf A Husain, Martina Huemer, Julia B Hennermann, Rahel Schuler, Andreas Hahn","doi":"10.3233/JND-230164","DOIUrl":"10.3233/JND-230164","url":null,"abstract":"<p><strong>Background: </strong>Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) was approved in Europe in 2006. Nevertheless, data on the long-term outcome of infantile onset Pompe disease (IOPD) patients at school age is still limited.</p><p><strong>Objective: </strong>We analyzed in detail cardiac, respiratory, motor, and cognitive function of 15 German-speaking patients aged 7 and older who started ERT at a median age of 5 months.</p><p><strong>Results: </strong>Starting dose was 20 mg/kg biweekly in 12 patients, 20 mg/kg weekly in 2, and 40 mg/kg weekly in one patient. CRIM-status was positive in 13 patients (86.7%) and negative or unknown in one patient each (6.7%). Three patients (20%) received immunomodulation. Median age at last assessment was 9.1 (7.0-19.5) years. At last follow-up 1 patient (6.7%) had mild cardiac hypertrophy, 6 (42.9%) had cardiac arrhythmias, and 7 (46.7%) required assisted ventilation. Seven patients (46.7%) achieved the ability to walk independently and 5 (33.3%) were still ambulatory at last follow-up. Six patients (40%) were able to sit without support, while the remaining 4 (26.7%) were tetraplegic. Eleven patients underwent cognitive testing (Culture Fair Intelligence Test), while 4 were unable to meet the requirements for cognitive testing. Intelligence quotients (IQs) ranged from normal (IQ 117, 102, 96, 94) in 4 patients (36.4%) to mild developmental delay (IQ 81) in one patient (9.1%) to intellectual disability (IQ 69, 63, 61, 3x <55) in 6 patients (54.5%). White matter abnormalities were present in 10 out of 12 cerebral MRIs from 7 patients.</p><p><strong>Conclusion: </strong>Substantial motor, cardiac, respiratory, and cognitive deficits are frequent in IOPD long-term survivors who started ERT before 2016. The findings of this study can be valuable as comparative data when evaluating the impact of newer treatment strategies including higher enzyme dosage, immunomodulation, modified enzymes, or early start of treatment following newborn screening.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"167-177"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}