Orphanet Journal of Rare Diseases最新文献

{"title":"Clinical characteristics of tumor-induced osteomalacia lesions in the neurocranium and intracranial structures.","authors":"Yushuo Wu, Xiang Li, Zhiqin Xu, Wei Lv, Zhixiang Wang, Xiaolin Ni, Qianqian Pang, Ruizhi Jiajue, Yue Chi, Wei Liu, Lijia Cui, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Wenbin Ma, Yu Wang, Yong Yao, Yi Guo, Zhiqiang Gao, Guodong Feng, Fang Qi, Yiyi Gong, Weibo Xia","doi":"10.1186/s13023-026-04477-1","DOIUrl":"10.1186/s13023-026-04477-1","url":null,"abstract":"<p><strong>Background: </strong>Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive fibroblast growth factor 23 (FGF23) secretion. However, TIO lesions located in the neurocranium (NC) and intracranial (IC) structures remain poorly characterized.</p><p><strong>Objective: </strong>To characterize the clinical features of TIO lesions in NC and IC structures and to compare them with those located in the sinuses.</p><p><strong>Methods: </strong>This retrospective study included patients diagnosed with TIO who underwent tumor resection at Peking Union Medical College Hospital between January 2016 and December 2023. Patients with lesions in NC and IC structures were defined as the study group, while those with sinus lesions served as the control group. Clinical characteristics, biochemical parameters, and surgical outcomes were systematically analyzed and compared between groups.</p><p><strong>Results: </strong>TIO lesions in NC and IC structures were distributed across the skull base, temporal region, sellar region, frontal lobe, and occipital region. Compared with sinus lesions, patients with NC and IC lesions showed comparable clinical and biochemical profiles but exhibited significantly worse outcomes, including higher rates of non-remission and tumor recurrence. These findings suggest increased difficulty in complete tumor resection and disease control in this subgroup.</p><p><strong>Conclusion: </strong>TIO lesions in NC and IC structures are associated with poorer surgical outcomes and higher recurrence rates despite similar baseline characteristics. These results highlight the need for improved localization strategies and tailored management approaches for this challenging subgroup.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405382","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":"Prevalence and cardiovascular phenotypes of dextrocardia and situs inversus among 277,396 adults: longitudinal evidence of amplified age-related blood pressure progression.","authors":"Dehao Zhang, Mei Lin, Xiaona Wang, Richard Liang, Michelle A Williams, Yi Ning","doi":"10.1186/s13023-026-04449-5","DOIUrl":"10.1186/s13023-026-04449-5","url":null,"abstract":"<p><strong>Background: </strong>Dextrocardia and situs inversus are rare congenital malformations. Although associated anomalies are well recognized, their prevalence in unselected adult populations and their cardiovascular phenotypes, particularly blood pressure in nonclinical settings, remain poorly characterized. This study aimed to estimate their prevalence, blood pressure profiles, and longitudinal changes in a large nonclinical cohort.</p><p><strong>Methods: </strong>In this longitudinal observational study, we reviewed records from the Beijing MJ health check-up cohort (2003-2025). Dextrocardia and situs inversus were confirmed via electrocardiography and imaging. Linear regression models assessed blood pressure differences, adjusting for age, sex, body mass index, glucolipid metabolism, renal function, and lifestyle factors. Linear mixed-effects models evaluated long-term blood pressure changes.</p><p><strong>Results: </strong>Among 277,396 adults, 43 had dextrocardia, 38 had situs inversus, and 29 had both. The prevalence (95% CI) was 1.6 (1.1-2.0) per 10,000 for dextrocardia and 1.4 (0.9-1.8) per 10,000 for situs inversus. In fully adjusted models, dextrocardia was associated with a 5.3 mmHg higher SBP (95% CI: 1.3-9.2) and a 4.5 mmHg higher DBP (1.7-7.4). Situs inversus was associated with a 7.0 mmHg higher SBP (2.8-11.2) and a 3.3 mmHg higher DBP (0.3-6.3). Longitudinally, each 10-year increase in age was associated with an additional 5.9 mmHg rise in SBP in dextrocardia (1.0-10.7; P for interaction = 0.02) and 5.5 mmHg in situs inversus (0.5-10.6; P for interaction = 0.03) compared with controls.</p><p><strong>Conclusion: </strong>In this large nonclinical cohort, dextrocardia and situs inversus were associated with higher blood pressure and a steeper age-related increase in SBP. Further studies are needed to confirm these findings.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405455","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":"Automated quantification of skin Gb3 load and white matter lesion assessment in Fabry disease.","authors":"Catharina Pfister, Magnus Schindehütte, Christoph Erbacher, Thomas Klein, Simone Rost, Aljosha Calvin Lang, Mirko Pham, Peter Nordbeck, Christoph Wanner, Claudia Sommer, Nurcan Üçeyler","doi":"10.1186/s13023-026-04490-4","DOIUrl":"10.1186/s13023-026-04490-4","url":null,"abstract":"<p><strong>Background: </strong>Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by cellular accumulation of globotriaosylceramide (Gb3).</p><p><strong>Methods: </strong>We investigated dermal Gb3 load as a potential surrogate marker for systemic FD manifestations by applying an automated image analysis pipeline to skin punch biopsies from the lower leg of 149 individuals carrying variants in GLA, the gene encoding alpha-galactosidase A. Variants were stratified by pathogenicity: Group 1 (pathogenic), Group 2 (non-pathogenic), and Group 3 (variants of unknown significance). Gb3 was visualized via Shiga toxin subunit B and quantified using CellProfiler (v4.1.3). Results were compared to healthy controls and patients with idiopathic small fiber neuropathy.</p><p><strong>Results: </strong>Dermal Gb3 load was elevated in both men and women with pathogenic GLA variants (Group 1, p < 0.001), excluding those with the N215S variant. Increased Gb3 deposition was associated with pain in men (p < 0.05), but not with overall disease severity, treatment status, or cerebral white matter lesions. Diagnostic sensitivity and specificity to correctly determine FD were 67% and 95% in men, and 78% and 81% in women, respectively.</p><p><strong>Conclusion: </strong>Our findings demonstrate the feasibility of automated dermal Gb3 quantification and its capacity to detect cutaneous Gb3 accumulation in pathogenic GLA variant carriers. However, its diagnostic accuracy is moderate, and it does not reliably reflect systemic involvement in FD.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405423","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":"Elamipretide in pediatric Barth syndrome: from heart failure to school return.","authors":"Pascal Amedro, Mathieu Andrianoely, Pauline Gohier, Justine Leroux, Nathalie Aladjidi, Stephanie Lagorce, Melissa Daccord, Marion Audie, Astrid Botte, Karine Nubret, Pascale Richard, Sandrine Roche, Delphine Lamireau, Candice Tetard, Aurelien Trimouille, Arielle Desir, Samir Mesli, Jean Donadieu, Julien Gotchac","doi":"10.1186/s13023-026-04487-z","DOIUrl":"10.1186/s13023-026-04487-z","url":null,"abstract":"<p><strong>Background: </strong>Barth syndrome (BTHS) is a rare X-linked mitochondrial disorder characterized by cardiomyopathy, neutropenia, and skeletal myopathy. Elamipretide is a mitochondria-targeting peptide that stabilizes cardiolipin and improves mitochondrial function. While use of this treatment in infants with BTHS has been reported in the United States, no cases have been described outside the US or in older children.</p><p><strong>Case presentation: </strong>We report the first case of a preschool-aged child with genetically confirmed BTHS and advanced heart failure, who was treated with elamipretide under a compassionate use program approved by the French Drug Administration (ANSM). At treatment initiation, this 5-year-old patient presented with severe left ventricular dysfunction (LVEF = 20%) and moderate-to-severe mitral regurgitation. He was dependent on gastrostomy feeding and had been listed for heart transplantation. Subcutaneous elamipretide (10 mg/day) was initiated alongside maximal conventional heart failure therapy. Over six months, LVEF improved to 50%, mitral regurgitation decreased to mild, Ross class improved from IV to I, and substantial gains were observed in functional capacity, nutritional status, and health-related quality of life (HRQoL). The patient returned to full-time school and remained temporarily suspended from the transplant list. Treatment was generally well tolerated. One transient, non-serious episode of abdominal pain with moderate pancreatic enzyme elevation occurred, which resolved without treatment discontinuation.</p><p><strong>Conclusions: </strong>This case suggests that elamipretide may improve cardiac function, exercise tolerance, nutrition, and HRQoL in preschool-aged pediatric BTHS patients, potentially delaying the need for transplantation. Broader pediatric evaluation is warranted. Further strategies, such as youth-tailored hybrid cardiac rehabilitation programs, could complement pharmacological therapy and further optimize outcomes in this population.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405400","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":"Triple A syndrome with a new mutation pattern, first documented case in Austria: a case report with literature review.","authors":"Karolina Anderle, Theresa Muellner-Bucsics, Alek Stadlmann, Clemens Gangl, Franco Laccone, David Horner, Safoura Sheikh Rezaei, Michael Trauner, Christian Mueller","doi":"10.1186/s13023-026-04465-5","DOIUrl":"10.1186/s13023-026-04465-5","url":null,"abstract":"<p><strong>Purpose: </strong>Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder, characterised by achalasia, alacrima, and adrenal insufficiency. The syndrome is caused by various mutations in the AAAS gene, encoding the protein ALADIN, leading to many heterogeneous clinical manifestations.</p><p><strong>Methods: </strong>We conducted a case-based literature review. The patient gave his informed consent prior to his inclusion in this study. All personal data was anonymised. This study was approved by the Ethics committee of the Medical University of Vienna and performed in accordance with the Declaration of Helsinki.</p><p><strong>Results: </strong>We report a case of a 51-year-old male patient with recurring symptoms of dysphagia due to achalasia, who was previously treated by Heller myotomy and repeated endoscopic dilations. He was diagnosed with primary adrenal insufficiency in childhood and substituted with fludrocortisone and hydrocortisone. The Schirmer test confirmed total alacrima, and neurological testing showed mild peripheral and central neuropathy. Genetic analysis was performed using PCR-amplification of the AAAS coding exons followed by sequencing. Long-read sequencing confirmed compound heterozygosity for two point mutations in the AAAS gene: a missense mutation, ENST00000209873.9:c.938T>A (p.Val313Asp) in exon 10, and a novel nonsense mutation, ENST00000209873.9:c.1264C>T (p.Gln422Ter) in exon 14.</p><p><strong>Conclusion: </strong>This is the first documented case of Triple A syndrome in Austria. Notably, some of the patient's characteristic symptoms presented unusually late in life. By utilising long-read sequencing, we experimentally confirmed the in trans orientation of a new mutation located at a previously described position and a novel nonsense variant. We strongly recommend genetic testing for patients presenting with at least two symptoms of the Triple A triad (achalasia, adrenal insufficiency, alacrima) or associated neurological symptoms, as clinical manifestations can be delayed.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405458","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":"Unraveling the psychological burden of Behçet disease: the impact of anxiety and depression on health-related quality of life outcomes.","authors":"Samar Tharwat, Mohamad Nassan, Nasim Jaber, Mo'min Khatib, Hamza Aljubaeh, Omar Abumunshar","doi":"10.1186/s13023-026-04433-z","DOIUrl":"10.1186/s13023-026-04433-z","url":null,"abstract":"<p><strong>Background: </strong>Behçet's disease (BD) is a chronic, inflammatory multisystem disease that has impact both physical health and mental well-being. However, the psychological impact of BD remains underexplored, particularly in Arabic-speaking populations. The aim of this study was to assess the prevalence of anxiety and depression in Arabic-speaking BD patients, evaluate their association with health-related quality of life (HRQoL), and identify key predictors of psychological distress in these patients.</p><p><strong>Methods: </strong>This cross-sectional study included 192 BD patients recruited from our rheumatology clinic and an online survey among BD patients. Psychological distress was assessed using the Arabic version of Hospital Anxiety and Depression Scale (HADS), while HRQoL was assessed via the Arabic version of Short Form 36 (SF-36) Health Survey. Univariate and multivariate regression analyses were performed to identify main factors linked with anxiety and depression.</p><p><strong>Results: </strong>Anxiety and depression were highly prevalent in BD patients, with 53.1% of the study participants exhibiting abnormal anxiety levels and 38.5% showing abnormal depression scores. Higher levels of psychological distress were statistically significantly associated with BD disease activity and elevated erythrocyte sedimentation rate levels (p = 0.017). Additionally, patients with greater anxiety and depression scores had significantly lower HRQoL scores across all SF-36 domains (p < 0.001). Gender differences were observed, with females showing higher anxiety rates (p = 0.006).</p><p><strong>Conclusions: </strong>Anxiety and depression are major contributors to reduced HRQoL in BD patients, necessitating a multidisciplinary approach that integrates mental health care into disease management.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405438","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 homocysteine levels in carriers with MMACHC gene variants.","authors":"Yi Ding, Yuxin Deng, Haijuan Zhi, Xia Zhan, Wenjun Ji, Zizhen Gong, Lili Hao, Lianshu Han","doi":"10.1186/s13023-026-04468-2","DOIUrl":"10.1186/s13023-026-04468-2","url":null,"abstract":"<p><strong>Objective: </strong>Variants in the MMACHC gene cause combined methylmalonic acidemia (MMA) and homocystinuria, cobalamin C (cblC) type. This study aimed to determine whether heterozygous MMACHC variant carriers exhibit elevated plasma homocysteine (Hcy) levels and to explore the variant-type-specific biochemical effects.</p><p><strong>Methods: </strong>In this prospective study, 301 MMACHC variant carriers and 304 controls were enrolled. Plasma Hcy levels, demographic characteristics, and clinical data were collected. Propensity score matching (PSM, 1:1) was performed to balance age and sex between groups. Generalized linear models were applied to investigate the correlation between MMACHC variant carriage and Hcy levels.</p><p><strong>Results: </strong>After PSM, 173 carrier-control pairs were included. Carriers showed significantly higher Hcy levels (median 12.27 µmol/L, range 5.30-85.90) than controls (9.80 µmol/L, 3.10-53.30; P < 0.001). Both Male sex (β = 7.816, 95% CI:5.746-9.887) and MMACHC variant carriage (β = 5.741, 95%CI:3.743-7.740) were independently associated with elevated Hcy. Among carriers, missense variants, especially c.80A > G (p.Q27R), were correlated with higher Hcy levels.</p><p><strong>Conclusion: </strong>Heterozygous MMACHC variant carriers had higher plasma Hcy levels than age- and sex-matched controls in this study. Missense variants and male sex tended to be associated with higher Hcy levels. These findings suggest that MMACHC variant carriers can present with biochemical abnormalities and associated with alterations in homocysteine metabolism.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405435","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":"Increased awareness around an ultra-rare disease can improve diagnosis delays: the French example in primary hyperoxalurias.","authors":"Lara Cabezas, Aurélie De Mul, Laurence Derain, Romain Pszczolinski, Cindy Castrale, Emmanuel Letavernier, Laurent Mesnard, Dominique Guerrot, Lise Allard, Olivia Boyer, Mélissa Ould Rabah, Isabelle Vrillion, François Nobili, Ariane Zaloszyc, Cécile Acquaviva, Justine Bacchetta, Sandrine Lemoine","doi":"10.1186/s13023-026-04463-7","DOIUrl":"10.1186/s13023-026-04463-7","url":null,"abstract":"<p><strong>Background: </strong>Primary hyperoxalurias (PH) are rare recessive autosomal genetic diseases inducing increased hepatic oxalate production. Apart from genetic background, their prognosis depends mainly on diagnosis delay. We recently reported shorter diagnosis delay in children compared with adults (1.2 (0.1-3.0) versus 30 (17-36) years) in a French PH cohort of 52 patients diagnosed between 2015 and 2019. In 2020, the first RNA interfering therapy was approved, leading to increased awareness and communication from reference centres, scientific societies and pharmaceutical companies. Our aim was to evaluate whether diagnosis delay was improved in this global setting.</p><p><strong>Methods: </strong>We performed a retrospective study including all consecutive patients that received a positive genetic test for PH in our expert genetic laboratory in Lyon between January 2020 and December 2024. We compared outcomes with the historical cohort. Diagnosis delay was defined by the time between the first symptoms and the result of genetic test.</p><p><strong>Results: </strong>In total, 62 patients (37 children) were included. Forty-two (78%) patients had PH type 1, 5 (8%) had PH2 and 11 (18%) had PH3. The diagnosis delay remained significantly shorter in children as compared to adults (0.75 (1.10) versus 15 (16.21) years, p < 0.05), but decreased in both sub-groups when compared to the previous study.</p><p><strong>Conclusions: </strong>The delay in PH diagnosis in France has been halved over the past five years. This improvement may be associated with recent therapeutic developments and increased awareness of the disease. Earlier diagnosis may enable earlier management, which might ultimately contribute to improved overall prognosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387957","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":"Patient-driven surveys of mucopolysaccharidoses revealed patient-reported outcomes in the Japan MPS patient and family group.","authors":"Toko Shibuya, Takeyuki Akiyama, Tetsuji Fujiyama, Takanobu Otomo","doi":"10.1186/s13023-026-04479-z","DOIUrl":"10.1186/s13023-026-04479-z","url":null,"abstract":"<p><strong>Background: </strong>Japan Mucopolysaccharidoses (MPS) Patient and Family Group (J-MPS) was founded in 1986. It is the largest patient group for all types of MPS in Japan and now includes some of the patients with lysosomal storage diseases. Patients receive medical care but suffer from the daily progression of symptoms, holding a different assessment of treatment effectiveness than that considered by the medical professionals. This study summarises the annual reports of the society and the results of periodic surveys conducted by their own. The 20-year annual reports are based on J-MPS membership records since 2005. The three questionnaire surveys were planned, designed, and conducted by the patient association own. Survey I was conducted mainly about treatment and activities of daily living with MPS I, II, IVA, and VI for which ERTs are available. Survey II asked about current symptoms and medical care with MPS IIIA and IIIB. Survey III was focused on ocular complications and skeletal symptoms with all types of MPS.</p><p><strong>Results: </strong>MPS II is the most common type of membership, and the average age of members is gradually increasing over the year. In MPS, age at diagnosis has decreased compared to previous surveys. Even though enzyme replacement therapy and hematopoietic stem cell transplantation have improved symptoms, there is a slight discrepancy between improvement and patient satisfaction. The degree of need for assistance in life varies with the disease type. Decreased bone mineral density and retinal pigmentary degeneration may be underestimated.</p><p><strong>Conclusions: </strong>This research is not physician-led evaluations, but patient-driven surveys, which is significant in that it focuses on the problems faced by patients and their families in the current era when enzyme replacement therapies are available. Coordination among patients, families, health care providers, and physicians is important to improve patients' quality of life.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382568","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":"Cognitive function in adult NF1 patients without other cognitive disorders: a cross-sectional study.","authors":"Daniel Muñoz, Juan Luis Becerra, Elisabeth Castellanos, Victoria Aran, Emilio Amilibia, Montse Pauta, Belén García, Andrea Ros, Ignacio Blanco, Mercè Jodar","doi":"10.1186/s13023-026-04456-6","DOIUrl":"10.1186/s13023-026-04456-6","url":null,"abstract":"<p><strong>Background: </strong>Neurofibromatosis type 1 (NF1) is associated with cognitive impairments affecting attention, executive function, memory, visuospatial abilities, and processing speed, which are well described in children and adolescents and may interfere with daily functioning. In contrast, cognitive functioning in adults with NF1 remains less clearly defined, particularly in individuals without previous neurological or psychological conditions affecting cognitive functioning that may confound neuropsychological performance. This cross-sectional study aimed to characterize cognitive performance across multiple domains in adults with NF1 and to examine the relationship between cognitive performance and psychological and clinical variables.</p><p><strong>Results: </strong>Eighty-seven adults with NF1 and no intellectual disability or previously diagnosed cognitive or psychiatric disorders underwent standardized neuropsychological assessment across seven cognitive domains commonly reported as affected in NF1, particularly in pediatric populations: visual memory, verbal memory, executive function, attention, visuospatial ability, working memory, and visuomotor speed. Participants also completed questionnaires assessing sociodemographic and psychological variables. Cognitive performance was standardized using age-adjusted normative Z-scores. Adults with NF1 performed below the normative mean across several cognitive domains relative to age-adjusted Spanish reference data. Executive function showed clinically significant impairment (z = -2.267), whereas attention showed low-average performance (z = -1.171). Although attention was associated with skin severity and visuospatial ability with depressive symptoms (p < 0.05), these associations were not significant after correction for multiple comparisons.</p><p><strong>Conclusions: </strong>These findings suggest a consistent pattern of cognitive underperformance in adults with NF1 without previous neurological or psychological conditions affecting cognitive functioning, supporting the presence of a specific cognitive vulnerability associated with the condition. Although some clinical factors showed associations with specific cognitive domains, these relations were small and did not remain significant after correction for multiple comparisons. These results highlight the importance of routine cognitive assessment and targeted cognitive and psychosocial support strategies, including their integration into genetic counseling, to improve clinical follow-up and patient care.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382499","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}