Orphanet Journal of Rare Diseases最新文献

{"title":"Global variations in diagnostic methods and epidemiological estimates in Pompe disease: findings from a scoping review.","authors":"Roberto Giugliani, Faryn Solomon, Hani Kushlaf, Erica Wright, Tmirah Haselkorn, Edmar Zanoteli, Benedikt Schoser","doi":"10.1186/s13023-025-03679-3","DOIUrl":"https://doi.org/10.1186/s13023-025-03679-3","url":null,"abstract":"<p><strong>Background: </strong>Pompe disease is caused by pathogenic variants in the GAA gene, resulting in lysosomal acid α-glucosidase (GAA) deficiency. The prevalence of Pompe disease is not well-defined, and estimates vary by geographic region. We evaluated the global epidemiology of Pompe disease and the potential reasons for differing prevalence estimates using published data from worldwide newborn screening (NBS) programs and population-based studies.</p><p><strong>Methods: </strong>A comprehensive literature search in PubMed was conducted in July 2023, updated in March 2024, and validated with an Embase search in June 2024. Search terms included Pompe disease, GSDII, prevalence, incidence, epidemiology, survival, mortality, and NBS. Studies were included based on robust epidemiological methods, the presence of disease definition, and publication within the past 5 years. We identified 1210 abstracts, of which 295 met recency criteria, 30 were deemed relevant, and 11 met all inclusion criteria.</p><p><strong>Results: </strong>Prevalence estimates and GAA enzyme activity cutoff values varied across geographic regions. In NBS studies, the birth prevalence of infantile-onset Pompe disease (IOPD) ranged from 1 in 297,387 in Japan to 1 in 62,186 in Taiwan, and late-onset Pompe disease (LOPD) ranged from 1 in 82,914 in Taiwan to 1 in 17,133 in Pennsylvania. Data from the French National Pompe Registry (N = 246) showed an increase in diagnosis of LOPD from 2.6/year before 2001 to 10.6/year during 2001-2010 and 12.8/year during 2011-2015. Enzyme cutoffs in dried blood spots varied from < 3% of lymphocyte mean to 2.10 μmol/L/h to ≤ 18% of the daily median. Three studies noted higher prevalence in populations of African descent, and two noted a higher frequency of pseudodeficiency alleles in Asian populations.</p><p><strong>Conclusions: </strong>This scoping review confirmed that prevalence estimates differ for IOPD and LOPD and vary by geographic region, potentially by race and ethnicity. It highlights the need to standardize screening and diagnosis methods, genetic testing protocols, and uniform disease classification between IOPD and LOPD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"216"},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040792","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":"Hereditary leptomeningeal transthyretin amyloidosis with heterozygous TTR mutation: a case report and literature review.","authors":"Hong-Tao Chen, You-Jun Tian, Jue Zhang, Bing-Rong Xiao, Ke Yang, Ya-Li Zhang","doi":"10.1186/s13023-025-03736-x","DOIUrl":"https://doi.org/10.1186/s13023-025-03736-x","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the clinical and neuroimaging features of hereditary leptomeningeal transthyretin amyloidosis (hATTR-LA), a dominant inheritance disorder caused by a heterozygous TTR gene mutation.</p><p><strong>Methods: </strong>A comprehensive retrospective evaluation was conducted, incorporating detailed clinical records, multimodal neuroimaging findings, and a systematic review of the literature to contextualize the observations.</p><p><strong>Results: </strong>The patient was a 55-year-old male who presented with chronic central nervous system symptoms, including sensory-motor peripheral neuropathy and progressive visual impairment. Cerebrospinal fluid analysis revealed elevated protein levels. Neuroimaging showed progressive leptomeningeal hyperdensity on CT and characteristic linear thickening with enhancement of the leptomeninges on MRI, involving both cerebral and spinal regions. Genetic testing confirmed the diagnosis by identifying a heterozygous c.265T > C (p.Y89H) pathogenic variant in exon 3 of the TTR gene, classified as pathogenic according to ACMG guidelines.</p><p><strong>Conclusion: </strong>Multimodal imaging provides valuable, non-invasive insights for diagnosing hATTR-LA, enhancing diagnostic accuracy and informing clinical management of this rare condition.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"213"},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032605","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":"Overall survival among patients with activated phosphoinositide 3-kinase delta syndrome (APDS).","authors":"Malena Mahendran, Julia E M Upton, Ramya Ramasubramanian, Heidi L Memmott, Guillaume Germain, Katharina Büsch, François Laliberté, Amanda Harrington","doi":"10.1186/s13023-025-03734-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03734-z","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to describe overall survival (OS) of patients with APDS relative to the global population as well as among subsets of patients with concurrent lymphoma or hematopoietic stem cell transplant (HSCT) relative to the overall APDS population.</p><p><strong>Methods: </strong>Patient-level data were extracted from a recent systematic literature review of 351 unique patients with APDS. OS was evaluated using the Kaplan-Meier method up to age 65 years. OS rate and corresponding 95% CI were reported at each decade of age. Global mortality estimates were obtained from World Health Organization life tables for 2019.</p><p><strong>Results: </strong>Of the 351 patients with APDS (APDS1, 267 [76.1%]; APDS2, 83 [23.6%]; unspecified, 1 [0.3%]), 41 (11.7%) died. The OS rate was 25.0% (95% CI, 1.6-62.7%) by the last death event at 64 years of age. Starting at 12 years of age, the OS rate was numerically lower in patients with APDS relative to the global population (median OS, 64 vs. 75 years, respectively). Relative to the overall APDS population, OS rates were numerically similar in those who underwent HSCT (median OS, 64 years for both; p = 0.569), whereas OS rates were numerically lower in patients with concurrent lymphoma (median OS, 41 vs. 64 years, respectively; p = 0.109). Publication bias in source data was a possible limitation.</p><p><strong>Conclusion: </strong>Reduced survival in patients with APDS suggests a high disease burden, particularly in those with concurrent lymphoma. These results highlight the unmet need for disease-modifying treatments for APDS.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"212"},"PeriodicalIF":3.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004001","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":"Comprehensive insights into pathogenesis, diagnosis, treatment, and prognosis in adult autoimmune enteropathy.","authors":"Muhan Li, Tianming Xu, Gechong Ruan, Chengzhu Ou, Bei Tan, Shengyu Zhang, Xiaoqing Li, Yan You, Weixun Zhou, Ji Li, Jingnan Li","doi":"10.1186/s13023-025-03731-2","DOIUrl":"https://doi.org/10.1186/s13023-025-03731-2","url":null,"abstract":"<p><p>Autoimmune enteropathy (AIE) constitutes a diverse array of disorders characterized by immune dysregulation and gastrointestinal manifestations, chiefly chronic diarrhea. Due to the small number of reported cohorts, the current knowledge and understanding of adult-onset AIE is rare compared with pediatric or syndromic AIE. Pathogenesis might involve genetic predisposition, aberrant immune homeostasis, comorbidities of autoimmune diseases and environmental trigger. Diagnosis relies on a comprehensive assessment encompassing clinical evaluation, laboratory tests, endoscopic findings and histopathological features, yet distinguishing AIE from other disorders with similar presentations poses diagnostic challenges. Treatment strategies predominantly center on immunosuppressive therapies, exhibiting varied efficacy among individuals. Supportive treatment and prevention and management of complications are also important for prognosis. The prospectives of future researches need to explore the genetic and immunological mechanism, the diagnostic modalities and the treatment strategies to improve patient outcomes.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"208"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039254","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":"Small intestinal bacterial overgrowth in variant transthyretin amyloidosis (A-ATTRv).","authors":"Ana Moreno García, Mireia Grimalt Oliver, Juan González-Moreno, María Antonia Ribot-Sansó, Eugenia Cisneros-Barroso, Inés Losada López","doi":"10.1186/s13023-025-03727-y","DOIUrl":"https://doi.org/10.1186/s13023-025-03727-y","url":null,"abstract":"<p><p>Variant transthyretin amyloidosis (A-ATTRv) can lead to sensory, motor, and autonomic neuropathy, as well as a variety of gastrointestinal (GI) disorders. While previous studies have explored gastrointestinal symptoms in A-ATTRv, no studies have definitively examined the role of bacterial overgrowth, such as SIBO, in exacerbating these symptoms. Identifying the presence of SIBO in A-ATTRv patients could lead to better-targeted treatments for gastrointestinal complications.We conducted a cross-sectional, unicentric observational pilot study, analysing the presence of SIBO using a lactitol breath test in 39 individuals carrying the V30M mutation: 21 asymptomatic carriers and 18 patients with A-ATTRv. We did not find a higher prevalence of SIBO, among patients with A-ATTRv compared to asymptomatic carriers. Though no significant relationship between SIBO and A-ATTRv was found, notable differences in gastrointestinal symptoms suggest these may be independent of SIBO. Furthermore, no relationship was found between the presence of SIBO and gender.Given the limitations of this pilot study, we did not find a relationship between A-ATTRv and intestinal microbiota disorders. Future research with larger sample sizes and more sensitive diagnostic tools is required to further explore this potential link.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"210"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972435","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":"Efficacy of different treatment strategies in patients with mucopolysaccharidosis: a systematic review and network meta-analysis of randomized controlled trials.","authors":"Lingling Huang, Jianru Wu, Biyu Tang, Jingying Wu, Fenfang Wei, Hong Qiao Li, Limin Li, Xinru Wang, Bei Wang, Wenyu Wu, Xiang Hong","doi":"10.1186/s13023-025-03735-y","DOIUrl":"https://doi.org/10.1186/s13023-025-03735-y","url":null,"abstract":"<p><p>This systematic review of randomized controlled trials (RCT) was conducted to evaluate the efficacy of enzyme replacement therapy (ERT) for patients with mucopolysaccharidosis (MPS). We systematically searched PubMed, Embase, Web of Science, and Cochrane databases up to August 22, 2023. Study design, interventions, and outcome data were extracted. Continuous variable random-effects network meta-analysis was performed. The review included 23 studies involving 1,047 people with MPS I-VI. In MPS I, urinary glycosaminoglycan (uGAG) level was significantly reduced in patients who took 2 mg/kg/week pentosan polysulfate (-2.66, 95% confidence interval (CI)[-3.86, -1.46]) compared with those who took 1 mg/kg/week. In MPS II, compared with the placebo group, significant reduction were observed in the uGAG (-270.77, 95% CI[-406.57, -139.71]) and the cerebrospinal fluid (CSF) GAG (-1,385.29, 95% CI[-2493.33, -392.65]). In MPS IV, 6-min walking test (6MWT) (40.82, 95% CI[16.19, 64.92]) and 3-min stair climb test (3MSCT) (16.07, 95% CI[12.16, 21.62]) were significantly increased in patients who took elosulfase alfa at a dose of 4.0 mg/kg/week compared with the placebo group. In MPS VI, recombinant human arylsulfatase B (rhASB) and galsulfase (1.0 mg/kg/week) significantly reduced uGAG aggregation compared with the placebo group (-217, 95% CI[-258, -176]) and galsulfase (2.0 mg/kg/week) group (-286.5, 95% CI[-436.5, -136.5]), respectively. Moreover, most studies had high (34.8%) or unclear (43.5%) risk of bias assessments and confidence assessment were low. ERT alleviated symptoms to some extent, but current evidence was insufficient. Hence, further evidence from large-sample RCT is needed.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"211"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998420","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":"Serum creatinine to cystatin C ratio as monitoring biomarker in Chinese adult spinal muscular atrophy: a prospective cohort study.","authors":"Sihui Chen, Qiong Wang, Jiajia Fu, Qianqian Wei, Ruwei Ou, Xiaohui Lai, Xueping Chen, Huifang Shang","doi":"10.1186/s13023-025-03730-3","DOIUrl":"https://doi.org/10.1186/s13023-025-03730-3","url":null,"abstract":"<p><strong>Background: </strong>The creatinine to cystatin C ratio (CCR) can be used as a biomarker of muscle mass and strength, but no studies have evaluated whether it can be used as a biomarker to monitor the efficacy of treatment with nusinersen in Chinese adults with 5q-associated spinal muscular atrophy (SMA).</p><p><strong>Methods: </strong>In this prospective observational study, 28 adult SMA patients were followed for 18 months. Data on motor function and daily activities were collected using the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walking Test (6WMT), and Barthel Index (BI). Serum levels of creatinine (Cr), creatine kinase (CK), and CCR were measured. Spearman correlation and linear mixed models analyzed the relationships between functional scores and laboratory indicators.</p><p><strong>Results: </strong>HFMSE scores showed significant improvement at Visit 5 (V5) [+ 1.04 points, p = 0.016), V6 (+ 1.61, p = 0.012), V7 (+ 1.93, p < 0.001), and V8 (+ 1.89, p < 0.001)], while RULM scores improved significantly at V5 (+ 2.00 points, p = 0.024), V7 (+ 2.00, p = 0.032), and V8 (+ 2.00, p < 0.001). The BI also exhibited significant improvement at V7 (+ 5.00, p < 0.001) and V8 (+ 2.50, p < 0.001). The 6MWT did not show significant improvement (p > 0.05). Serum CCR levels were significantly higher than baseline at V5 (+ 4.35 points, p < 0.001), V7 (+ 5.12, p < 0.001), and V8 (+ 6.59, p < 0.001). Cr levels were significantly higher than baseline at V5 (+ 2.39 points, p < 0.001) and V7 (+ 0.90, p < 0.001), while log10 CK levels remained unchanged (p > 0.05). Spearman correlation analysis revealed CCR showed the strongest correlation with functional scores, followed by Cr and log10 CK. Further linear mixed-effect model indicated that after adjusting for covariates, only CCR showed a dynamic positive correlation with HFMSE scores (β = 0.280; 95% CI 0.023-0.537, p = 0.033), while other serum indicators had no correlation with functional scores.</p><p><strong>Conclusion: </strong>Long-term use of nusinersen effectively improves motor function and quality of life in adult SMA patients, and CCR may be a better indicator to reflect changes in motor function during treatment compared to other blood biomarkers.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"209"},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008013","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":"Assessing osteopenia and osteoporosis with dual-energy x-ray absorptiometry studies in Fabry disease.","authors":"Alyaa Shmara, Grace Lee, Mania Mgdsyan, Kathy Hall, Nadia Sadri, Angela Martin-Rios, Kelsey Valentine, Tatiana Kain, Madeleine Pahl, Lynda E Polgreen, Virginia Kimonis","doi":"10.1186/s13023-025-03601-x","DOIUrl":"https://doi.org/10.1186/s13023-025-03601-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Fabry disease (FD) is a rare multi-systemic lysosomal storage disease that affects the heart and kidneys most significantly. An underappreciated manifestation of FD is reduced bone mineral density. Currently, there are no specific guidelines for routine bone density assessments, and treatment of osteoporosis and osteopenia in FD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;To ascertain the frequency of low bone mineral density in FD we studied dual-energy x-ray absorptiometry (DXA) scans obtained as part of routine care from a cohort of 25 individuals followed at the University of California-Irvine Medical Center for the period 2008-2023. The most recent BMD results for the lumbar spine and femoral neck were collected from 12 males and 13 females to examine the prevalence of low bone mineral density. The lowest Z- and/or T-scores of either lumbar spine or femoral neck were selected for analysis. Demographic factors, disease and ERT status, and other laboratory values were collected concurrently (within ± 9 months) with DXA scan results and were analyzed with Z- and T-scores to assess for correlations. In our cohort the mean age was 51 years (median 56 years, range 18-77 years). The Z-scores for all participants and T-scores from postmenopausal women and men ≥ 50-year-old were analyzed and correlated with various measures including disease duration, BMI, renal function (measured by eGFR), plasma GL3, Lyso-GL3, calcium, vitamin D, and alkaline phosphatase levels. These parameters were concurrent with DXA scan results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The average Z-score for all the participants was -1.2 ± 1.3 (range -4.6 to 1.6). Twenty-four percent of all participants (n = 6) had significantly low Z-scores ≤ -2.0. To identify the frequency of subjects with osteopenia, defined as T-score between -1.0 and -2.5 and osteoporosis defined as T-score &lt; -2.5, T-scores were analyzed in postmenopausal women (n = 8) and men 50 years and older (n = 7). Of these 15 individuals, average T-score was -2.2 ± 1.3 (range -5.4 to 0.3), and 86.7% (n = 13) had abnormal results (osteopenia and osteoporosis), 53.3% (n = 8) had osteoporosis and 33.3% (n = 5) had osteoporosis. We found a significant difference in Z-scores between male (-1.98 ± 1.33) and female patients (-.45 ± 0.82) t (23) = 3.487 (p =  &lt; 0.001). We did not find any differences in z-scores between different ethnic backgrounds. There was a strong negative correlation between Z-scores and Lyso-GL3 levels [r (15) = -.72, p = .001] and a moderate positive correlation between Z-scores and body mass index (BMI) [r (23) = .43, p = .033]. No correlation was found between Z-scores and calcium levels. There is a strong negative correlation between T-scores and Lyso-GL3 levels [r (8) = -.86, p = .001] and a negative correlation between T-scores and participants' ages at the time of DXA [r (13) = -.57, p = 0.028]. There is a positive correlation between T- scores and calcium levels [r ","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"206"},"PeriodicalIF":3.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040715","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":"A comprehensive update of genotype-phenotype correlations in PMM2-CDG: insights from molecular and structural analyses.","authors":"Tiago Oliveira, Ricardo Ferraz, Luísa Azevedo, Dulce Quelhas, João Carneiro, Jaak Jaeken, Sérgio F Sousa","doi":"10.1186/s13023-025-03669-5","DOIUrl":"https://doi.org/10.1186/s13023-025-03669-5","url":null,"abstract":"<p><p>PMM2-CDG (phosphomannomutase 2-deficiency) is the most prevalent N-glycosylation disorder and results from impairments of PMM2 activity. This disease presents a large variety of pathogenic variants, which cause a wide phenotypical spectrum. This diversity, together with the low number of affected patients, raises the challenge of determining genotype-phenotype correlations in PMM2-CDG. This type of correlation could be highly significant in determining disease progression, prognosis, severity and in developing genome-personalized therapies. Structural analyses offer a valuable approach for assessing the pathogenic mechanisms within the PMM2 protein structure at a molecular level. Such an approach can reveal novel insights into the consequences of missense variants and their relationship with patients'phenotype. In this comprehensive review, we evaluate at a structural level 41 missense mutations in PMM2-CDG, examining their phenotypical characteristics and clinical severity, protein properties and interference at the enzymatic level. This work broadens the understanding of the intricate relationships between genotype and clinical manifestations of PMM2-CDG.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"207"},"PeriodicalIF":3.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993080","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":"European experience of steroid therapy in children with developmental and epileptic encephalopathy with spike wave activation in sleep ((D)EE-SWAS).","authors":"Dilan Canbay, Floor E Jansen, Jan Schönberger, Victoria San Antonio-Arce, Julia Jacobs, Kerstin Alexandra Klotz","doi":"10.1186/s13023-025-03725-0","DOIUrl":"https://doi.org/10.1186/s13023-025-03725-0","url":null,"abstract":"<p><strong>Background: </strong>Developmental and epileptic encephalopathy with spike wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) are rare but well-known childhood epileptic disorders. Steroids are one of the first line treatment options, but a variety of steroid regimens exists. The aim of this survey was to evaluate the practices of steroid therapy in the treatment of (D)EE-SWAS across European centers.</p><p><strong>Methods: </strong>An online survey was conducted (via 'SurveyMonkey' Europe) among European epilepsy centers. Questions asked included: characteristics of replying center, applied definition of DEE-SWAS, existence of regional/national guidelines regarding diagnostic and therapeutic management. Particular attention was paid to the indication/contraindication of steroids and treatment regimens used.</p><p><strong>Results: </strong>Responses were obtained from 60 centers across 18 countries. Only 15% of centers reported the availability of national guidelines for the management of (D)EE-SWAS. There were variations in definition of (D)EE-SWAS, with Spike-Wave- Index (SWI) > 85 (irrespective of cognitive status) and SWI > 50% with concurrent neurodevelopmental regression being the most prevalent, reported in 36% and 50%, respectively. Steroids and clobazam were considered the predominant treatment options, with the primary indication for steroids being neurodevelopmental arrest (52%) and failure of clobazam treatment (51%). Treatment goals of steroid treatment primarily focused on neurodevelopmental improvement (95%), and reduction of SWI (66%). Methylprednisolone and prednisone were the most frequently used steroids, although other steroid types were also reported. Pulse therapy was utilized exclusively in 47% of centers. The most commonly used steroid regimen was intravenous/oral methylprednisolone pulse therapy (20 mg/kg/day for 3 days, either monthly or weekly), although a broad variety of different regimens were reported. Criteria influencing decisions about steroid treatment were largely based on personal experience, with scientific publications playing a role in decision-making in only 14% of centers.</p><p><strong>Conclusion: </strong>Steroids are part of the first line therapy of (D)EE-SWAS across Europe, but heterogeneity in formulations, dosages, and regimens persists due to limited guideline availability. The absence of comparative studies and the discordant definitions of (D)EE-SWAS further hinder comparisons of treatment efficacy. We recommend that harmonizing steroid treatment strategies is imperative for optimizing (D)EE-SWAS management.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"204"},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037559","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}