Orphanet Journal of Rare Diseases最新文献

{"title":"The RaDiCo information system for rare disease cohorts.","authors":"Paul Landais, Sonia Gueguen, Annick Clement, Serge Amselem","doi":"10.1186/s13023-025-03629-z","DOIUrl":"https://doi.org/10.1186/s13023-025-03629-z","url":null,"abstract":"<p><strong>Background: </strong>Rare diseases (RDs) clinical care and research face several challenges. Patients are dispersed over large geographic areas, their number per disease is limited, just like the number of researchers involved. Current databases as well as biological collections, when existing, are generally local, of modest size, incomplete, of uneven quality, heterogeneous in format and content, and rarely accessible or standardised to support interoperability. Most disease phenotypes are complex corresponding to multi-systemic conditions, with insufficient interdisciplinary cooperation. Thus emerged the need to generate, within a coordinated, mutualised, secure and interoperable framework, high-quality data from national or international RD cohorts, based on deep phenotyping, including molecular analysis data, notably genotypic. The RaDiCo program objective was to create, under the umbrella of Inserm, a national operational platform dedicated to the development of RD e-cohorts. Its Information System (IS) is presented here.</p><p><strong>Material and methods: </strong>Constructed on the cloud computing principle, the RaDiCo platform was designed to promote mutualization and factorization of processes and services, for both clinical epidemiology support and IS. RaDiCo IS is based on an interoperability framework combining a unique RD identifier, data standardisation, FAIR principles, data exchange flows/processes and data security principles compliant with the European GDPR.</p><p><strong>Results: </strong>RaDiCo IS favours a secure, open-source web application in order to implement and manage online databases and give patients themselves the opportunity to collect their data. It ensures a continuous monitoring of data quality and consistency over time. RaDiCo IS proved to be efficient, currently hosting 13 e-cohorts, covering 67 distinct RDs. As of April 2024, 8063 patients were recruited from 180 specialised RD sites spread across the national territory.</p><p><strong>Discussion: </strong>The RaDiCo operational platform is equivalent to a national infrastructure. Its IS enables RD e-cohorts to be developed on a shared platform with no limit on size or number. Compliant with the GDPR, it is compatible with the French National Health Data Hub and can be extended to the RDs European Reference Networks (ERNs).</p><p><strong>Conclusion: </strong>RaDiCo provides a robust IS, compatible with the French Data Hub and RDs ERNs, integrated on a RD platform that enables e-cohorts creation, monitoring and analysis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"166"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Undifferentiated autoinflammatory disease in adults: a prospective study in 61 patients.","authors":"Junke Miao, Di Wu, Min Shen","doi":"10.1186/s13023-025-03685-5","DOIUrl":"https://doi.org/10.1186/s13023-025-03685-5","url":null,"abstract":"<p><strong>Backgrounds: </strong>Undifferentiated or undefined systemic autoinflammatory disease (uSAID) encompasses a group of rare, heterogeneous diseases characterized by the features of well-defined systemic autoinflammatory diseases (SAIDs), but lacking diagnostic phenotypes or genetic confirmation. We aimed to describe the phenotypes, genotypes and treatment responses of Chinese adult patients with uSAID.</p><p><strong>Methods: </strong>The final diagnosis of uSAID was reached in 61 patients, whose organ-specific inflammation was compared and three subgroups were identified based on phenotypic similarities to well-defined SAIDs. Phenotypes, genotypes and treatment responses were analyzed in these subgroups.</p><p><strong>Results: </strong>Among the 61 uSAID patients, 17 had disease-onset during childhood, and 44 had adult-onset. Compared to those without pulmonary manifestations, patients with pulmonary involvement exhibited higher frequencies of myalgia, skin lesions, cardiac involvement, gastrointestinal involvement, urinary involvement, lymphadenopathy, headache, and intellectual impairments. Twenty-four patients exhibited monogenic SAID-like phenotypes, 12 had polygenic SAID-like phenotypes, and the remaining 25 were categorized as having atypical phenotypes. Among the 53 patients followed, 25% (13/53) improved spontaneously with complete or partial recovery independent of therapy. Patients with atypical phenotypes had the highest spontaneous remission rate (10/23, 43%).</p><p><strong>Conclusion: </strong>This study is the first to describe the clinical and genetic features of a cohort of Chinese adult patients with uSAID. Patients with pulmonary manifestations may be more prone to developing complex phenotypes, while those with atypical phenotypes have a high rate of spontaneous remission, indicating a favorable prognosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"165"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and health burden of 20 rare neurological diseases in South China from 2016 to 2022: a hospital-based observational study.","authors":"Jingjing Li, Shujin Tang, Jiaoxing Li, Xin Huang, Yu Liu, Jinsheng Zeng, Yuhua Fan","doi":"10.1186/s13023-025-03704-5","DOIUrl":"https://doi.org/10.1186/s13023-025-03704-5","url":null,"abstract":"<p><strong>Background: </strong>Rare neurological diseases (RNDs) result in severe health burdens worldwide. Data from China are limited. We aimed to investigate the health burden of 20 RNDs in Guangdong Province (GD), which contains two-thirds of the population of South China.</p><p><strong>Methods: </strong>The hospitalization data of 20 RNDs were described using hospital-based front sheet data from 3,037 hospitals of GD from 2016 to 2022. The 20 RNDs included amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth Disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, congenital myotonia, congenital myasthenic syndrome, Dravet syndrome, Fabry disease, hereditary spastic paraplegia, Huntington disease, Leber hereditary optic neuropathy, mitochondrial encephalopathy (ME), multi-focal motor neuropathy, myotonic dystrophy, primary hereditary dystonia, progressive muscular dystrophy (PMD), spinal and bulbar muscular atrophy, spinal muscular atrophy (SMA), spinocerebellar ataxia, Wilson disease (WD) and X-linked adrenoleukodystrophy. Age were presented as mean and standard deviation while length of hospital stay as median and interquartile range (25th and 75th percentiles). The other variables were described as number and percentage. The data were analyzed by Joinpoint regression.</p><p><strong>Results: </strong>There were 9,351 cases, including 330 ICU and 155 death cases. The average age was 33.7 ± 22.0 y, and 63.8% of patients were male. From 2016 to 2022, the number of RND (and juvenile RND) cases were 1034 (184), 1174 (293), 1443 (374), 1422 (320), 1331 (337), 1432 (409) to 1515 (515). ICU (and juvenile ICU) cases rose from 28 (3), 34 (6), 24 (4), 38 (11), 46 (13), 54 (24) to 106 (56). Joinpoint regression showed significant upward trend in percentages of juvenile and juvenile ICU cases (APC = 8.13, P< 0.05; APC = 28.42, P< 0.05). The fop five RNDs were WD, ASL, PMD, ME, and SMA, which accounted for 79.7% of all, 99.1% of ICU, and 94.8% of death cases.</p><p><strong>Conclusions: </strong>We demonstrated that the increase in health burden of RNDs was mainly evident in juveniles in South China from 2016 to 2022. The top 5 RNDs accounted for majority of the critical patients.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"163"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular genetic characteristics of pediatric PFIC3 patients: three novel variants and prognosis for parental liver transplantation.","authors":"Jiqiang Hu, Chenyu Yang, Bingqian Tan, Qiang Xiong, Ying Le, Jianyang Hu, Haoming Wang, Xiaoke Dai, Mingman Zhang","doi":"10.1186/s13023-025-03670-y","DOIUrl":"https://doi.org/10.1186/s13023-025-03670-y","url":null,"abstract":"<p><p>Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3) is a rare inherited liver disease caused by a mutation in the ABCB4 gene, leading to dysfunction of multidrug resistance protein 3 (MDR3). The earlier the onset of PFIC3 in children is, the more severe the prognosis. The diagnosis of PFIC3 is typically based on clinical symptoms, laboratory tests, and imaging assessments, with final confirmation requiring genetic testing. The aim of this study was to investigate the associations between genetic mutations in PFIC3 and clinical features, molecular genetics, and liver histopathology to improve early recognition and understanding of this disease. By analysing the data of three children with PFIC3 who underwent parental liver transplantation, we were able to gain a deeper understanding of the complexity and diversity of the disease. With respect to molecular genetics, we identified five mutation sites in the ABCB4 gene, including three newly discovered mutations. Immunohistochemical analysis revealed reduced expression of the MDR3 protein in child 1 and no expression in child 2 or child 3, revealing an intrinsic link between the ABCB4 gene and the MDR3 protein. Histopathologically, all three patients presented with significant portal vein fibrosis or cholestatic liver cirrhosis. In conclusion, this study emphasizes the importance of molecular genetic and pathological evaluation of patients with PFIC3 mutations and elucidates the impact of these three mutations on the course of the disease in children, for whom early symptomatic treatment and early preparation for liver transplantation are options worth considering.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"164"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower respiratory rate during sleep in children with angelman syndrome compared to age-matched controls.","authors":"Leo Gschwind, Sebastian Camillo Holst, David Nobbs, Florian Lipsmeier, Katalin Buzasi, Ponghatai Boonsimma, Alexander Rotenberg, Vitaliy Kolodyazhniy, Jörg Felix Hipp","doi":"10.1186/s13023-025-03553-2","DOIUrl":"https://doi.org/10.1186/s13023-025-03553-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder caused by the absence of a functional UBE3A gene, leading to developmental, behavioral, and medical challenges. Sleep disturbances, including sleep-disordered breathing, are common in AS. This study, for the first time, investigates nocturnal respiration in individuals with AS and healthy controls at home in a long term setting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A non-invasive ballistocardiography-based (BCG) sleep monitoring device (\"sleep mat\") placed under the participants' mattresses, was used to remotely monitor children with AS aged 1 to 12 years (6.0 ± 3.2 years, n = 40) and age-matched typically developing controls (TDC) (6.2 ± 3.5 years, n = 20) for approximately 12 months. The sleep mat recorded physiological signals during times in bed. We applied fast-Fourier transformation (FFT) to exclude segments without a clear respiratory signal, thereby minimizing the impact of large body movements, wakefulness, or seizure activity. Moreover, polysomnography (PSG) was collected for up to three nights for each participant in their home. Clinical characteristics, genotype, and Bayley Scales of Infant and Toddler Development&lt;sup&gt;®&lt;/sup&gt; (Bayley-III) were also analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The average median BCG-derived respiratory rate over the entire study duration was significantly lower in AS compared to TDCs (Cohen's d = 1.31). PSG-derived respiration data corroborated the lower breathing rate in AS (Cohen's d = 0.77) and revealed a strong correlation between BCG and PSG derived respiration (r = 0.85) and thus a strong convergent validity of the sleep mat against \"gold standard\" measures. Next, we defined two groups of AS individuals based on their respiratory rates: a normal respiration group with rates above the minimum in TDC, and a low respiratory rate group with rates below the TDC group's minimum. A higher prevalence of respiratory abnormalities was observed in deletion carriers (55.2%) versus non-deletion carriers (9.1%). Pulse oximetry data indicated lower oxygen saturation levels in AS individuals (Cohen's d = 1.60). Moreover, lower Bayley-III scores were observed in the low respiration group, suggesting a link between respiratory dysfunction and neurodevelopmental outcomes in AS. Medication use, particularly antiepileptic drugs, was found to suppress respiratory rates, highlighting the complex interplay between concomitant medication use, genotype, and sleep in AS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study provides the first long-term observational evidence of a persistent bradypnea-like phenotype in individuals with AS, which may have significant implications for their clinical management. The successful use of the sleep mat device as a non-invasive physiological ambulatory monitoring tool demonstrates its potential as a digital health technology for detecting respiratory abnormalities in pediatric neurodevelopmental diso","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"167"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of asfotase alfa on fracture healing of adult patient with hypophosphatasia and literature review.","authors":"Songqi Wang, Lei Sun, Jing Hu, Qian Zhang, Ou Wang, Yan Jiang, Weibo Xia, Xiaoping Xing, Mei Li","doi":"10.1186/s13023-025-03663-x","DOIUrl":"10.1186/s13023-025-03663-x","url":null,"abstract":"<p><strong>Objective: </strong>Hypophosphatasia (HPP) is a rare inherited disorder caused by ALPL gene mutations, with fracture nonunion being a serious complication. This study investigated the effects of teriparatide and asfotase alfa (AA) on femoral fracture healing of an adult patient with HPP, accompanied with a literature review.</p><p><strong>Methods: </strong>A 37-year-old woman wheelchair-bound was diagnosed with HPP due to an extremely low serum alkaline phosphatase (ALP) level (4-10 U/L), who suffered from bilateral femur pain and non-union of femoral shaft fractures on both sides. Compound heterozygous missense mutations (c.382G > A and c.461C > T) were identified in exon5 of ALPL gene. The patient received teriparatide sequential AA therapy. Serum levels of ALP, β-isomerized carboxy-telopeptide of type I collagen (β-CTX) and procollagen type 1 amino-terminal peptide (P1NP), bone mineral density (BMD) and skeletal X-ray were measured during the treatment. Literature was searched by keywords of \"Hypophosphatasia\", \"HPP\", \"ALPL\", \"TNSALP\", \"ALP\" combined with \"Asfotase alfa\", \"AA\", \"enzyme replacement therapy\", and \"ERT\".</p><p><strong>Results: </strong>After unsuccessful 6-month teriparatide treatment for femoral fracture, AA treatment was initiated, at a dose of 2 mg/kg, 3 times a week. After the first month of AA treatment, serum ALP level increased from 4 to 9206 U/L, and serum calcium and phosphate levels decreased, with increase in PTH, β-CTX, and P1NP levels. After 4 months of AA treatment, her bone pain significantly alleviated, accompanied by significant shortening of the fracture line. After 10 months of AA therapy, the fracture demonstrated complete healing and the patient could walk independently. BMD at lumbar spine and hips was significantly increased. Among 295 adult patients with HPP reported in the literature, 213 (72.2%) exhibited skeletal-related symptoms and 91 (30.8%) presented with bone fractures. In addition to skeletal manifestations, the patients presented with early tooth loss, muscle weakness and ectopic calcification. AA treatment, spanning 9 weeks to 3 years, has been shown to increase ALP levels, promote fracture healing, improve mobility, and alleviate bone pain.</p><p><strong>Conclusion: </strong>Adult HPP patients mainly present with recurrent or poorly healing fractures, bone pain, and early loss of teeth. AA replacement therapy can effectively promote fracture healing, relieve bone pain, and enhance mobility.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"162"},"PeriodicalIF":3.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795884","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 the pathogenicity of novel GNE mutations and clinical, pathological, and genetic characteristics of GNE myopathy in Chinese population.","authors":"Yingming Xing, Lingqian Zhao, Renlong Zhao, Qiyun Liu, Juan Wang, Le Wang, Wei Zhang, Junhong Guo, Rongjuan Zhao, Xueli Chang","doi":"10.1186/s13023-025-03696-2","DOIUrl":"10.1186/s13023-025-03696-2","url":null,"abstract":"<p><strong>Background: </strong>GNE myopathy is a rare autosomal recessive distal myopathy caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), a bifunctional enzyme critical for sialic acid biosynthesis. This study aimed to describe a novel autosomal recessive GNE pedigree in a Chinese family and explore the possible mechanism of GNE variants in GNE myopathy, the most common distal myopathy in China. The clinical, genetic, and pathological characteristics of 216 Chinese patients with GNE myopathy were also summarized.</p><p><strong>Methods: </strong>The proband and her family underwent a comprehensive medical history assessment and neurological examinations. Whole-exome sequencing was performed on the proband, and Sanger sequencing was performed on family members. 293T cell lines were used for immunofluorescence (IF), Western blot, and dual-luciferase reporter assays. We collected the clinical data of 216 GNE myopathy patients from previous reports up until August 1, 2024. Patients were classified into distinct groups according to mutation location to analyze genotype-phenotype correlation.</p><p><strong>Results: </strong>Whole-exome sequencing of the proband and Sanger sequencing of all available family members identified a compound heterozygous mutation involving a novel promoter region mutation, c.-259T > C, and a reported mutation, c.88 C > T (p.Q30*). The GNE promoter fragment (-500 to -1; c.-259T > C) was cloned to construct the firefly luciferase reporter vector. The dual-luciferase reporter assay showed that the mutated promoter exhibited reduced transcriptional activity, resulting in decreased GNE expression. Western blot and IF analysis of overexpressing Q30* revealed that it reduced GNE expression without altering cellular localization and increased the ectopic cytoplasmic expression of TDP-43. The p.D207V mutation was the most common variant in China. Patients carrying p.D207V tended to experience later disease onset. In the epimerase/epimerase group, men experienced earlier disease onset than women (p < 0.05). In other groups, age at disease onset in females was earlier than that in males.</p><p><strong>Conclusions: </strong>The c.-259T > C mutation decreases promoter activity, while the c.88 C > T (p.Q30*) mutation reduces GNE expression and affects TDP-43 distribution, thus affecting normal cellular function. The p.D207V mutation is the most common GNE variant in China and is associated with milder disease progression.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"161"},"PeriodicalIF":3.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788772","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":"The wide phenotypic spectrum of thiamine metabolism dysfunction syndrome 5 and its treatment.","authors":"Alice Dallan, Giuseppe Reynolds, Carlotta Canavese, Diana Carli, Maria Luca, Andrea Gazzin, Marco Spada, Francesco Porta, Alessandro Mussa","doi":"10.1186/s13023-025-03665-9","DOIUrl":"10.1186/s13023-025-03665-9","url":null,"abstract":"<p><p>Thiamine metabolism dysfunction syndrome 5 (TMDS5) is a rare inborn error of metabolism caused by variants in TPK1, leading to reduced TPK levels. This enzyme is crucial for the production of thiamine pyrophosphate, the active form of thiamine, a vital coenzyme in numerous metabolic pathways. The clinical presentation exhibits a diverse range of manifestations. In this review, we explore reported cases in the literature and present two cases representing the extremes of the clinical spectrum: recurrent ataxia and Leigh syndrome. The former phenotype follows a milder course. The second one is characterized by early onset and severe symptoms, including dystonia, epilepsy, and developmental regression, progressing rapidly to severe disability with high mortality. Typically, children exposed to infectious or traumatic triggers display episodes marked by ataxia and dystonia, with periods of good health or only mild disabilities in between. Treatment with the phosphorylated thiamine active bioform, TPP, is more effective in the recurrent ataxia form, especially when initiated promptly at symptom onset. Further studies are needed to identify available biomarkers and establish correlations between different variants, severity, and treatment response.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"160"},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788774","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":"Growth differentiation factor 15: a valuable biomarker for the diagnosis and prognosis of late-onset form of multiple Acyl-CoA dehydrogenation deficiency.","authors":"Sun Yuan, Tang Shuyao, Lyu Jingwei, Wen Bing, Xu Jingwen, Li Busu, Zhao Bing, Ji Kunqian, Yan Chuanzhu","doi":"10.1186/s13023-025-03651-1","DOIUrl":"10.1186/s13023-025-03651-1","url":null,"abstract":"<p><strong>Background: </strong>Multiple acyl-CoA Dehydrogenation Deficiency (MADD) is a hereditary metabolic disorder affecting the metabolism of fatty acids, amino acids, and choline, typically presenting with fat accumulation and mitochondrial abnormalities in muscle pathology. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine implicated in energy metabolism. Therefore, this study aimed to assess the level of GDF15 in patients with late-onset MADD and to evaluate its potential as a reliable biomarker for diagnosing symptoms and determining the severity of late-onset MADD.</p><p><strong>Methods: </strong>In this study, consecutive patients with MADD mitochondrial diseases were recruited from the Neuromuscular Center of Qilu Hospital, Shandong University, between April 2015 and October 2021. We measured serum GDF15 levels in patients with late-onset MADD and healthy controls. Additionally, we analyzed the messenger RNA(mRNA) expression of GDF15 and integrated stress response (ISR)-related factors, including CHOP, ATF5, and TRIB3, in the muscles.</p><p><strong>Results: </strong>Serum GDF15 levels in patients with late-onset MADD were 18.8 times higher than those in healthy controls. GDF15 levels decreased as the disease progressed, and its elecated levels correlated with anorexia symptoms. The mRNA expression of GDF15 and ISR-related factors in the muscles was higher in patients with late-onset MADD than in controls.</p><p><strong>Conclusion: </strong>GDF15 levels were significantly elevated in symptomatic patients with late-onset MADD, likely due to mitochondrial dysfunction activating the ISR pathway. These findings suggest that GDF15 is a valuable biomarker for monitoring disease severity and symptomatology in patients with late-onset MADD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"159"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780905","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":"Deep learning assisted retinal microvasculature assessment and cerebral small vessel disease in Fabry disease.","authors":"Yingsi Li, Xuecong Zhou, Junmeng Li, Yawen Zhao, Yujing Yuan, Bo Yang, Jingjing Xu, Qijie Wei, Xiaoming Yan, Wei Zhang, Yuan Wu","doi":"10.1186/s13023-025-03627-1","DOIUrl":"10.1186/s13023-025-03627-1","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to assess retinal microvascular parameters (RMPs) in Fabry disease (FD) using deep learning, and analyze the correlation with brain lesions related to cerebral small vessel disease (CSVD).</p><p><strong>Methods: </strong>In this retrospective case control study, fundus images from 27 FD patients and 27 age- and sex-matched healthy subjects were collected. RMPs, encompassing diameter, density, symmetry, bifurcation, and tortuosity, were quantified. Laboratory examination results, Mainz severity score index (MSSI) scores, and a brain magnetic resonance imaging scan for CSVD scores were extracted and their relationships with RMPs was analyzed.</p><p><strong>Results: </strong>Utilizing artificial intelligence-assisted analysis, compared with controls, FD patients exhibited reduced diameter (p = 0.001 for central retinal artery equivalent, p = 0.049 for central retinal vein equivalent), density (p < 0.001 for vessel area density, p = 0.001 for length density), fractal dimension (p < 0.001), and heightened arteriolar and venular asymmetry ratios (p = 0.002 and p = 0.037, respectively), venular curvature tortuosity (p = 0.037), and simple tortuosity (p = 0.037) in retinal microvascular networks. Gender-based differences in RMPs were observed among FD patients. Furthermore, RMPs were significantly associated with disease markers such as plasma globotriaosylsphingosine and α-galactosidase A activity, as well as MSSI scores. Notably, there was a significant negative correlation between the arteriolar asymmetry ratio and CSVD-related scores (age-related white matter changes: r =  - 0.683, p = 0.001; Fazekas: r =  - 0.673, p = 0.001; Lacuna: r =  - 0.453, p = 0.045; small vessel diseases: r =  - 0.721, p = 0.012; global cortical atrophy: r =  - 0.582, p = 0.009).</p><p><strong>Conclusions: </strong>Fabry disease patients demonstrated increased vascular tortuosity and asymmetry, reduced density and diameter, and a simpler fractal dimension in retinal microvasculature. These microvascular characteristics may serve as preliminary indicators for assessing brain lesions and could represent potential novel biomarkers for CSVD, aiding in the monitoring of FD severity and progression.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"158"},"PeriodicalIF":3.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780850","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}