Orphanet Journal of Rare Diseases最新文献

{"title":"Novel POMT2 variants associated with limb-girdle muscular dystrophy R14: genetic, histological and functional studies.","authors":"Guiguan Yang, Xiaoqing Lv, Wenjing Wu, Guangyu Wang, Mengqi Yang, Yifei Feng, Chuanzhu Yan, Meirong Liu, Pengfei Lin","doi":"10.1186/s13023-025-03578-7","DOIUrl":"10.1186/s13023-025-03578-7","url":null,"abstract":"<p><strong>Background: </strong>The POMT2 gene, which encodes protein O-mannosyltransferase 2, is essential for α-dystroglycan glycosylation. Variants in POMT2 cause various disorders, including the relatively rare presentation of limb-girdle muscular dystrophy R14 (LGMDR14).</p><p><strong>Methods: </strong>This study retrospectively analyzed the clinical, pathological, and genetic data of three LGMDR14 patients. And we investigated the pathogenic mechanisms of POMT2 variants through aberrant mRNA processing analysis and molecular dynamics simulations to assess their impact on protein structure and function.</p><p><strong>Results: </strong>We recruited three LGMDR14 patients from unrelated Chinese families, all presenting with adult-onset proximal muscle weakness. All of these patients showed a myopathic pattern on electromyography and decreased α-dystroglycan expression on muscle biopsy. One patient had severe cardiomyopathy and mild cognitive impairment. Genetic sequencing revealed compound heterozygous variants in the POMT2 gene in all three patients: c.1006 + 1G > A and c.295 C > T in patient 1, c.1261 C > T and c.700_701insCT in patient 2, and c.812 C > T and c.170G > A in patient 3. Variants c.700_701insCT, c.812 C > T, and c.170G > A are novel. Splicing and cDNA analysis revealed that the c.1006 + 1G > A variant could cause retention of the first 26 bp of intron 8 by inducing recognition of new donor splice sites. Pyrosequencing revealed that both frameshift variant c.700_701insCT and splicing variant c.1006 + 1G > A triggered a nonsense-mediated mRNA decay. Molecular dynamics indicated that c.1006 + 1G > A, c.700_701insCT, and c.170G > A variants could lead to truncated proteins, altering stability and function.</p><p><strong>Conclusions: </strong>Our study summarizes the clinical, pathological and genetic characteristics of three adult-onset LGMDR14 patients, expanding the genetic spectrum of POMT2 variants. Moreover, the finding reinforces the impact of POMT2 splicing defects on mRNA regulation, and molecular dynamics simulations predict the structural consequences of POMT2 variants, providing additional evidence for their functional effects.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"99"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of hereditary transthyretin amyloidosis in patients with suspected chronic inflammatory demyelinating polyneuropathy unresponsive to intravenous immunoglobulins: results of a retrospective study.","authors":"Yann Péréon, David Adams, Jean-Philippe Camdessanché, Jean-Baptiste Chanson, Pascal Cintas, Laurent Magy, Aïssatou Signaté, Guilhem Solé, Juliette Svahn, Céline Tard, Cyrla Hababou, Shahram Attarian","doi":"10.1186/s13023-025-03589-4","DOIUrl":"10.1186/s13023-025-03589-4","url":null,"abstract":"<p><strong>Background and aims: </strong>Hereditary transthyretin amyloidosis (ATTRv) should be considered in patients diagnosed with intravenous immunoglobulin (IVIg)-resistant chronic inflammatory demyelinating polyradiculoneuropathy (IVIg-NR CIDP). In this 1-year long, retrospective, multicentric study, an online questionnaire was sent to 1100 French healthcare professionals (HCPs) investigating: (i) how many IVIg-NR CIDP patients they followed; (ii) how many IVIg-NR CIDP patients had undergone TTR gene analysis; and (iii) how many IVIg-NR CIDP patients were eventually diagnosed with ATTRv. The questionnaire was sent every 3 months for 1 year and contained information on ATTRv clinical manifestations and diagnosis.</p><p><strong>Results: </strong>One-hundred and ten (10%) HCPs responded. A total of 2131 patients with CIDP were identified, including 315 (22.1%) with IVIg-NR CIDP. TTR gene analysis was performed in 144 patients and was positive in 43 cases (29.9%).</p><p><strong>Conclusions: </strong>This study demonstrates that ATTRv should be investigated systematically in patients diagnosed with IVIg-NR CIDP. HCP-directed information campaigns are useful for modifying diagnostic practices.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"95"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early oxytocin treatment in infants with Prader-Willi syndrome is safe and is associated with better endocrine, metabolic and behavioral outcomes.","authors":"Marion Valette, Gwenaelle Diene, Mélanie Glattard, Julie Cortadellas, Catherine Molinas, Sandy Faye, Grégoire Benvegnu, Kader Boulanouar, Pierre Payoux, Jean-Pierre Salles, Catherine Arnaud, Sophie Çabal, Maithé Tauber","doi":"10.1186/s13023-025-03560-3","DOIUrl":"10.1186/s13023-025-03560-3","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin (OT) plays an important role in modulating behavior, social interactions and feeding. Prader-Willi syndrome (PWS), a rare genetic neurodevelopmental disorder, is a model of hypothalamic disorder including OT dysfunction. We previously showed that infants with PWS who had received an early short course (7 days) of intranasal OT treatment improved their oral and social skills. We aim to document the long-term tolerance and effects of early intranasal OT treatment on the disease trajectory.</p><p><strong>Methods: </strong>We performed a comparative clinical trial including the 17 children who had received OT as infants in our previous study and compared them to 17 PWS non-exposed children at 3-4 years old. Primary endpoint was the total communication score on the Vineland Adaptive Behavior Scales-2nd edition (VABS-II). Secondary endpoints were the other domains of VABS-II, behavior scored by the Child Behavior Checklist, feeding skills, endocrine and metabolic profiles, and brain connectivity on functional magnetic resonance imaging.</p><p><strong>Results: </strong>We documented the long-term safety of early OT treatment. The VABS-II communication score was not different between the two groups, defined as OT-exposed and non-exposed, whereas a trend toward a higher socialization score was found in the OT-exposed children (p = 0.06). Circulating IGF-1 and HDL cholesterol were significantly higher in the OT-exposed group (p < 0.05). OT-exposed children had normal acylated ghrelin levels, which were lower than those observed in non-exposed children (p = 0.06), and they displayed higher connectivity of the orbitofrontal cortex brain region.</p><p><strong>Conclusion: </strong>Early OT treatment in infants with PWS is safe up to 3-4 years of age. OT-exposed children display better social, endocrine and metabolic outcomes. This study documents for the first time in human the biological window of opportunity of early OT treatment, which may change the trajectory of the PWS condition.</p><p><strong>Trial registration: </strong>Clinical trial NCT03081832 Retrospectively registered https://clinicaltrials.gov/search?cond=NCT03081832 .</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"96"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health outcomes following COVID-19 infection and vaccination in hereditary hemorrhagic telangiectasia.","authors":"Christopher M Tarulli, Xiayi Ma, Kamalprit Chokar, Nicholas T Vozoris, Marianne S Clancy, Marie E Faughnan","doi":"10.1186/s13023-025-03561-2","DOIUrl":"10.1186/s13023-025-03561-2","url":null,"abstract":"<p><strong>Background: </strong>There has been concern that individuals living with Hereditary Hemorrhagic Telangiectasia (HHT) could be at higher risk for poor outcomes if infected with SARS-CoV2, the virus that causes COVID-19 disease. As literature is lacking on outcomes on COVID-19 infection and vaccination in HHT, the objectives of this study were to determine and assess outcomes in HHT, as well as quantify vaccination rates and vaccination side effects in a large cohort of individuals with HHT.</p><p><strong>Method: </strong>Individuals previously recruited to OUR HHT Registry at St. Michael's Hospital, Toronto were contacted for participation in this study. Data were collected during annual assessment through a series of questionnaires asking specifically about HHT complications, treatments, and symptom management, along with COVID infection and vaccination data.</p><p><strong>Results: </strong>We attempted to contact all 262 subjects recruited to the registry. Of these, 215 (82.1%) responded at least once regarding COVID-19 related inquiries between April 2020 and August 2022, and these individuals formed our study sample. Forty-nine COVID-19 infections were reported in 47/215 (21.9%) individuals. Among 47 patients with recorded COVID-19 infection, 2/47 (4.3%) required urgent care and 7/47 (14.9%) were hospitalized following infection. Of the 7 individuals who were hospitalized, 3 (42.9%) required new supplemental oxygen. Zero deaths were reported due to COVID-19 infection. COVID vaccination history was available in 147/215 (68.4%). Of these, 135/147 (91.8%) of individuals reported vaccination and side effects were mild.</p><p><strong>Discussion: </strong>While our sample population is much like the general HHT population with regards to gender, HHT symptoms, and genetics, study limitations including survivor bias, lack of vaccine effectiveness assessment, and participant reported data should be acknowledged.</p><p><strong>Conclusion: </strong>Our results suggest that HHT patients are not at higher risk of severe infection with COVID-19 compared to the general population. Vaccination rates are high with only mild side effects being observed.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"94"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute hepatic porphyria in Denmark; a retrospective study.","authors":"Magnus Emil Ulrich Wagner, Morten Frost, Jan Frystyk","doi":"10.1186/s13023-025-03536-3","DOIUrl":"10.1186/s13023-025-03536-3","url":null,"abstract":"<p><strong>Background: </strong>Acute hepatic porphyria (AHP) constitutes a class of rare diseases caused by reduced function in enzymes of the heme-biosynthetic pathway. AHP includes acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP) and the extremely rare δ-aminolevulinic-dehydrase deficiency porphyria (ADP). This retrospective study describes characteristics of the Danish AHP patient population.</p><p><strong>Methods: </strong>Department of Endocrinology at Odense University Hospital serves as national AHP center. We performed a 5-year retrospective description of our AHP cohort using electronic patient journals. We included general symptoms, number of acute attacks, hospitalization rates, long-term sequelae and symptoms, and grouped patients according to creatinine-adjusted urinary baseline excretion (i.e., outside attacks) of the porphyrin precursor porphobilinogen (PBG) in normal-, moderate- and high-excretion and unknown.</p><p><strong>Results: </strong>The cohort contained 129 AHP patients, hereof 100 AIP, 12 HCP and 17 VP. Median age was 46.3 (32.1-62.0) years, and 85 (65.9%) were female. During the 5-years, 38 (29.5%) patients experienced symptoms. Hereof, 20 patients were hospitalized with acute attacks or chronic symptoms and treated with human hemin (n = 14). Most frequently reported symptoms were abdominal pain, nausea, vomiting, and neurological disturbances. Symptoms were more common in patients with high PBG baseline excretion (n = 39) as compared to those with moderate (n = 31) or normal (n = 40) PBG excretion (p = 0.002). Furthermore, females dominated the symptomatic group (68.4%).</p><p><strong>Conclusion: </strong>As reported internationally, AHP is more commonly diagnosed and symptomatic in women, and AIP was the most frequent AHP subtype. Those with an elevated urinary baseline PBG secretion were more likely to report AHP-related symptoms.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"93"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients.","authors":"Nina Vodnjov, Andraž Cerar, Aleš Maver, Borut Peterlin, Karin Writzl","doi":"10.1186/s13023-025-03613-7","DOIUrl":"10.1186/s13023-025-03613-7","url":null,"abstract":"<p><strong>Background: </strong>Titin truncating variants (TTNtv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare TTNtv-s in the constitutively expressed exons of the A-band of the protein titin are associated with DCM according to the guidelines, however, studies in large cohorts of patients with DCM suggest that the region where TTNtv-s are associated with DCM is wider, extending at least into the I-band. The aim of this study was to describe the molecular pathology of TTNtv-s in Slovenian patients with cardiomyopathy and to clinically characterise the most recurrent TTNtv.</p><p><strong>Results: </strong>We collected all TTNtv-s identified in patients with cardiomyopathy using next-generation sequencing genetic testing between 2010 and July 2024, resulting in 42 unique variants identified in 54 patients. The TTN:c.12478del variant, affecting not the A-band but the proximal I-band, specifically the cardiac-specific N2Bus region, was found to be the most recurrent variant, present in seven (11.6%) probands with DCM. Genetic characterisation revealed a probable founder origin of the variant. Clinical characterisation of these probands revealed a phenotype consistent with DCM and severely reduced left ventricular ejection fraction in all probands. Three (43%) of the probands had atrial fibrillation and/or non-sustained ventricular tachycardia. Based on literature reports and evidence supporting the pathogenicity of the TTN:c.12478del variant affecting the proximal I-band, we classified all rare TTNtv-s in constitutively expressed exons of the I-band as (likely) pathogenic. Therefore, 33 (78.6%) TTNtv-s were classified as (likely) pathogenic (13 in the I-band, affecting 19 probands and 20 in the A-band affecting 25 probands), meaning that TTNtv-s were identified in 44 genotype-positive Slovenian probands with DCM, explaining 73.3% of the molecular pathology of DCM.</p><p><strong>Conclusion: </strong>We report an almost threefold higher diagnostic yield of TTNtv-s in probands with DCM compared to previously reported findings in cohorts of patients with DCM from other populations. We also highlight the need for screening for rare TTNtv-s in the constitutively expressed exons of the I-band and for TTN:c.12478del in patients with DCM in this geographical region.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"92"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of SMN protein in umbilical cord blood and postnatal peripheral blood of neonates with SMA: a rationale for prompt treatment initiation to prevent SMA development.","authors":"Noriko Otsuki, Tamaki Kato, Mamoru Yokomura, Mari Urano, Mari Matsuo, Emiko Kobayashi, Kazuhiro Haginoya, Hiroyuki Awano, Yasuhiro Takeshima, Toshio Saito, Kayoko Saito","doi":"10.1186/s13023-025-03597-4","DOIUrl":"10.1186/s13023-025-03597-4","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disease caused by insufficient functional survival motor neuron protein (SMN). The SMN expression level in the spinal cord is highest during the 2nd trimester of the foetal period. We previously reported the SMN spot analysis in peripheral blood using imaging flow cytometry (IFC) as a biomarker of functional SMN protein expression. In this study, we analysed neonatal cord blood, postnatal peripheral blood, and maternal peripheral blood in presymptomatic five infants whose sibling has type 1 SMA to estimate prenatal and postnatal SMN dynamics before the onset of severe SMA.</p><p><strong>Results: </strong>Data from 37 untreated patients with SMA showed that SMN-spot⁺ cells were significantly correlated with SMA clinical classification and the copy numbers of the SMN2 gene. The range of values for cord blood, converted from each SMN2 copy number statistics, was - 0.7 to + 2.0 standard deviation (SD) (0.1-24.0%) for SMN-spot⁺ cells in patients with SMA. Subsequent analyses of the peripheral blood of neonates ranged from - 0.8 to + 0.8 SD (0.4-15.2%). The analysis of each maternal blood, converted from carrier statistics, ranged from - 0.2 to + 2.4 SD (1.4-25.2%). A correlation was observed between the cord blood and maternal peripheral blood.</p><p><strong>Conclusions: </strong>This study suggests that the status of the motor neuron pool in the spinal cord can be presumed by cord blood SMN-spot⁺ cells and that SMN protein depletion determines the timing of disease onset. As the SMN spot analysis values tended to decrease with time after birth, they may eventually lead to the development of SMA. Furthermore, a correlation was found between the SMN spot analysis values of neonatal cord blood and maternal blood, which predicts disease severity after birth. In other words, the SMN protein supplied from the mother to the foetus may suppress the development of SMA in the infant at birth, and depletion of the SMN protein may occur after birth, causing the infant to develop SMA. Our findings demonstrated the effectiveness of newborn screening and the potential of maternally mediated treatment strategies by providing a rationale for prompt treatment initiation in SMA.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"91"},"PeriodicalIF":3.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 economic burden of achondroplasia in the United States: results from a retrospective, observational study.","authors":"Nadia Merchant, Jose Alvir, Paulette Negron Ericksen, Jane Loftus, Jose Francisco Cara, Alison Slade, Michael P Wajnrajch, Christine L Baker","doi":"10.1186/s13023-024-03268-w","DOIUrl":"10.1186/s13023-024-03268-w","url":null,"abstract":"<p><strong>Background: </strong>Achondroplasia, a disease characterized by disproportionate short stature and increased morbidity, affects daily function and quality of life over the lifetime of the individual. However, data are limited on its economic impact, especially related to healthcare resource utilization (HCRU) and associated costs. This study aimed to characterize the clinical and economic impact of achondroplasia in the US relative to matched non-achondroplasia controls stratified by pediatric and adult populations.</p><p><strong>Methods: </strong>This retrospective study used data from the IQVIA PharMetrics Plus national claims database from January 2008 to December 2021. Individuals diagnosed with achondroplasia (index event) between July 2008 and December 2020 were matched on age and sex (1:2 ratio) to non-achondroplasia controls. General comorbidities were evaluated in the pediatric and adult populations. All-cause HCRU and direct medical costs were determined for the 12-month post-index period; out-of-pocket (OOP) costs were also determined. Study variables were analyzed using descriptive statistics.</p><p><strong>Results: </strong>A total of 530 individuals with achondroplasia (47.7% pediatric and 52.3% adults) were matched with 1,060 controls. Individuals in the achondroplasia cohort had higher overall comorbidity burdens than controls. HCRU was higher in the achondroplasia cohort relative to controls, with outpatient visits the most frequently used resource. Inpatient visits were the primary driver of mean (SD) total costs, which were 14-fold higher than controls ($28,386 [$259,858] vs $2,031 [$5,418]) in pediatric individuals, and 4-fold higher in adults $21,579 [$58,817] vs $4,951 [$13,020]); prescriptions accounted for 4.7% and 7.4% of total costs in the pediatric and adult achondroplasia cohorts, respectively. The OOP costs were approximately 3-fold higher in both pediatric and adult individuals with achondroplasia relative to controls.</p><p><strong>Conclusions: </strong>Individuals with achondroplasia are characterized by a higher comorbidity burden and substantially higher HCRU and related costs relative to matched controls. The results also suggest that despite high HCRU and costs, individuals with achondroplasia likely are not seen by providers early enough nor are they necessarily seen by appropriate specialists, indicating a need for improved care and disease management.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"90"},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'You constantly have to be switched on': A qualitative interview study of parents of children with STXBP1-related disorders in the Netherlands.","authors":"Sietske A L van Till, Sybren Sybesma, Hilgo Bruining, Matthijs Verhage, Eline M Bunnik","doi":"10.1186/s13023-024-03314-7","DOIUrl":"10.1186/s13023-024-03314-7","url":null,"abstract":"<p><strong>Background: </strong>Disorder-related variants in the STXBP1 gene are increasingly detected in children with severe developmental disorders. It is commonly acknowledged that developmental disorders significantly impact family life, but little is known about the day-to-day experiences of caregivers living with children with STXBP1-related disorders (STXBP1-RD). This knowledge gap may hinder researchers and care professionals from aligning research activities, care, and support with the perspectives of parents.</p><p><strong>Methods: </strong>We conducted a semi-structured interview study to gain a better understanding of the impact of having a child with STXBP1-RD on daily family life. Interviews were audio-recorded, transcribed, and analyzed thematically. We developed an 'analytical framework based on verbs', as verbs signify action, to present our results on the experiences of parents in everyday life.</p><p><strong>Results: </strong>We conducted 16 interviews with 21 parents of children with STXBP1-RD (2 to 18 years old), living in the Netherlands. The respondents described their caregiving responsibilities as extremely intense and demanding. They reported being constantly occupied with caring for their child, and expressed a feeling of always being 'switched on'. Parents' experiences are described using the following five verbs: (1) caring for their child, (2) recognizing their child's needs and having their child's needs recognized, (3) searching for answers and suitable care, (4) balancing delivering care while preserving other domains of life, and (5) coping with emotional impacts.</p><p><strong>Conclusions: </strong>This study shows how parenting a child with STXBP1-RD involves continuous engagement with both child-related care responsibilities and other activities, such as arranging suitable care and coping with emotional impacts. The accumulation of these responsibilities and challenges significantly impacts the everyday lives of the entire family. To support STXBP1 patient families, a broad approach is needed, focusing not only on developing new medical treatments, but also on improving other therapies (e.g., speech therapy or physiotherapy) and providing social support for the entire family, including emotional support, assistance with administrative tasks, and improved information provision after diagnosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"89"},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world analysis of the efficacy and safety of nusinersen in pediatric patients with spinal muscular atrophy.","authors":"Wenjing Li, Qin Zhang, Hongjun Miao, Jin Xu","doi":"10.1186/s13023-025-03603-9","DOIUrl":"10.1186/s13023-025-03603-9","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a rare neurodegenerative disease that significantly affects multiple systems in children. Nusinersen, the first approved treatment for SMA, enhances SMN protein production by targeting the RNA splicing site of the SMN2 gene, thus improving motor function. However, the high cost of nusinersen treatment raises concerns about its economic feasibility.</p><p><strong>Methods: </strong>This study retrospectively analyzed clinical data of 42 pediatric SMA patients treated with nusinersen from January 2022 to October 2024 at our hospital. We assessed the efficacy, safety, and economic impact of nusinersen in different SMA types. Motor function was evaluated using the CHOP-INTEND, HINE-2, HFMSE, and RULM scales. Safety was assessed based on adverse reactions and events, and economic evaluation considered total treatment costs and average cost per injection.</p><p><strong>Results: </strong>Nusinersen significantly improved motor function in SMA patients, especially in type I patients, who showed notable increases in CHOP-INTEND and HINE-2 scores. The RULM score had the highest increase among type II patients, while improvements were relatively lower in type III patients. Regarding safety, the incidence of adverse events was 40.48%, with fever being the most common adverse reaction, occurring in 36.36% of cases. Economic analysis indicated that the total treatment cost was highest for type III patients, though the cost differences among types were not statistically significant (P > 0.05).</p><p><strong>Conclusion: </strong>Nusinersen demonstrated significant clinical efficacy and favorable safety in pediatric SMA patients, with improved economic feasibility after insurance coverage. Our findings support early SMA screening and presymptomatic nusinersen administration to maximize therapeutic benefits. Further multicenter, large-sample, long-term follow-up studies are warranted to validate and expand upon these findings.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"87"},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}