Orphanet Journal of Rare Diseases最新文献

{"title":"Persistently low serum alkaline phosphatase in adults: prevalence and clinical characteristics in a large tertiary care hospital.","authors":"Fahad Alshahrani, Sara Alsuliman, Reema Alkalefah, Shaden Almutairi, Yara Aleidi, Mohammed Almohaya","doi":"10.1186/s13023-026-04493-1","DOIUrl":"10.1186/s13023-026-04493-1","url":null,"abstract":"<p><strong>Background: </strong>Alkaline phosphatase (ALP) plays an essential role in skeletal mineralization and bone metabolism. While elevated ALP levels are commonly investigated in clinical practice, persistently low ALP values are often overlooked despite their potential association with hypophosphatasia (HPP), a rare metabolic bone disorder caused by pathogenic variants in the ALPL gene. This study aimed to determine the prevalence and clinical characteristics of adults with persistently low ALP in a large tertiary care hospital.</p><p><strong>Methods: </strong>We conducted a retrospective review of adult patients who underwent serum ALP testing at King Abdulaziz Medical City, Riyadh, between January 2017 and December 2024. Patients with ≥ 2 ALP measurements < 40 IU/L separated by at least 30 days were identified. Secondary causes of low ALP were excluded through review of clinical history, laboratory data, and medication records. Demographic, clinical, biochemical, and imaging data were analyzed.</p><p><strong>Results: </strong>Among 243,362 adults with 928,403 ALP measurements, 7,307 patients (3.0%) had at least one ALP value < 40 IU/L. A total of 179 patients had ≥ 2 ALP measurements < 40 IU/L. After excluding 154 patients with secondary causes or incomplete data, 25 patients were identified with unexplained persistently low ALP (0.01% of the total tested population). The mean age was 52.2 years (range 18-92), and 68% were female. The mean nadir ALP was 30.2 IU/L. Musculoskeletal (MSK) symptoms (92%) and fatigue (79%) were the most common clinical manifestations, followed by dental abnormalities (50%), anxiety (33%), and depression (29%). Fractures were reported in 46% of patients, most commonly affecting the vertebrae, hips, and metatarsals. In subgroup analysis, patients with MSK symptoms had significantly lower nadir ALP levels (p = 0.021). Familial clustering of persistently low ALP was observed in 25% of patients. Notably, none of the reviewed electronic medical records documented recognition of persistently low ALP or consideration of hypophosphatasia.</p><p><strong>Conclusion: </strong>Persistently low ALP is uncommon but clinically relevant. Many affected patients demonstrated clinical features compatible with possible adult hypophosphatasia, and familial clustering suggests a possible genetic contribution. Greater awareness of this biochemical finding may improve recognition of potential HPP, prevent inappropriate antiresorptive therapy, and facilitate earlier diagnostic evaluation, including biochemical and genetic testing.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497813","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":"French national diagnosis and care protocol (PNDS) for infantile idiopathic hypercalcemia (IIH).","authors":"Cyril Amouroux, Valérie Porquet-Bordes, Elodie Adler, Yoan Le Goff, Justine Bacchetta, Jean Philippe Bertocchio, Gilles Cambonie, Marie Courbebaisse, Odile Dicky, Thomas Edouard, Barbara Girerd, Vincent Guigonis, Fairouz Halitim, Pascal Houiller, Agnès Linglart, Emeline Marquant, Denis Morin, Jean Pierre Salles, Anya Rothenbuhler","doi":"10.1186/s13023-026-04483-3","DOIUrl":"10.1186/s13023-026-04483-3","url":null,"abstract":"<p><p>The objective of this study was to establish a French National Diagnosis and Care Protocol (PNDS: Protocole National de Diagnostic et de Soins), with the aim of providing health professionals with free, open access synthesis on optimal management and care of patients with Infantile Idiopathic Hypercalcemia (IIH) ( https://www.has-sante.fr/jcms/p_3522489/fr/hypercalcemie-infantile-idiopathique-hii ). The process involved a critical review of the literature and a multidisciplinary expert consensus. IIH is a rare genetic disorder, with a prevalence estimated at 1 in 33,000. Its clinical manifestations (such as urinary stones or nephrocalcinosis) can appear at different ages. The pathophysiology of IHH is characterized by excessive 1,25(OH)2 vitamin D mediated dietary digestive calcium absorption. The underlying mechanism varies depending on the pathogenic variant involved, which is located in one of two genes, CYP24A1 or SLC34A1. The natural history and pathophysiology of IHH remain poorly understood and are underreported in the literature. Management of the disease varies according to the presentation and severity of hypercalcemia. Non-specific management strategies encompass the cessation of calcium intake, the discontinuation of native vitamin D supplementation, hyperhydration, and the occasional utilization of bisphosphonates. The necessity for long-term treatment, which may encompass both non-specific measures and specific interventions, depends on the severity and the genetic variant identified. Long-term follow-up appears essential, although there is limited data available, particularly for detecting complications of the disease, with nephrocalcinosis being the primary one.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471997","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":"Evaluating the relationship between antidrug antibodies and efficacy and safety outcomes in patients with Fabry disease receiving enzyme replacement therapy: a systematic literature review.","authors":"Patricio Aguiar, John A Bernat, Derralynn Hughes","doi":"10.1186/s13023-026-04438-8","DOIUrl":"10.1186/s13023-026-04438-8","url":null,"abstract":"<p><strong>Background: </strong>Fabry disease is a lysosomal storage disorder caused by deficient activity of the enzyme α-galactosidase A, resulting in progressive accumulation of globotriaosylceramide (Gb3) and widespread tissue and organ damage. Enzyme replacement therapy (ERT) can slow disease progression but may elicit antidrug antibody (ADA) responses. The impact of ADA status on long-term ERT efficacy and safety remains incompletely understood.</p><p><strong>Objective: </strong>We conducted a systematic literature review (SLR) to examine the impact of ADA status on outcomes in patients with Fabry disease receiving ERT. We aimed to evaluate associations between ADA status and specific outcomes, and to identify remaining evidence needs.</p><p><strong>Methods: </strong>Systematic searches were conducted in MEDLINE and Embase (up to March 4, 2025), supplemented by searches of the Cochrane Library and clinical trial registries. Eligible publications reported data on the relationship between ADA status and Fabry disease-related biomarkers (Gb3, globotriaosylsphingosine [lyso-Gb3]), efficacy (renal and cardiovascular) outcomes, and safety (adverse events [AEs] and infusion-related reactions [IRRs]) outcomes.</p><p><strong>Results: </strong>Of 1763 articles screened, 24 were included (19 reported disease-related biomarkers, 10 renal outcomes, 4 cardiovascular, and 9 AE/IRR data). Most analyses of disease-related biomarkers (17/18) reported statistically significant positive associations (p < 0.05) between ADA positivity and elevated biomarkers: plasma lyso-Gb3 (4/8 studies), plasma Gb3 (1/3 studies), and urine Gb3 (6/6 studies). Some renal data sets (2/9) reported evidence suggesting a potential association between more rapid decline in estimated glomerular filtration rate in ADA-positive (vs ADA-negative) patients. Four out of 9 studies reported statistically significant associations between ADA positivity and IRR occurrence; most studies stratifying IRR rates by ADA status (5/7) reported higher rates among ADA-positive (vs ADA-negative) subgroups.</p><p><strong>Conclusion: </strong>This SLR found evidence that ADA positivity may be associated with increased IRR risk and may have a negative effect on some measures of ERT efficacy. Inconsistencies in the identified data were likely driven by study design differences, including prior ERT exposure, follow-up time, and ADA assessment protocols. Additional prospective studies with standardized ADA assessments and accounting for patient baseline characteristics and disease severity, are needed to better understand the clinical implications of ADA formation on ERT outcomes, including an assessment of causality.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471987","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 genetic analysis of patients with Sjögren-Larsson syndrome in China.","authors":"Feng Chen, Bowen Yu, Yangshuo Wang, Liu Yuan, Liwei Zhang, Tinghong Liu, Feng Zhai, Jinshan Xu, Xin Ni, Shuli Liang","doi":"10.1186/s13023-026-04489-x","DOIUrl":"10.1186/s13023-026-04489-x","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the clinical features and genetic spectrum of Chinese patients with Sjögren-Larsson syndrome (SLS).</p><p><strong>Methods: </strong>We retrospectively reviewed genetically confirmed SLS cases managed in the Functional Neurosurgery Department of Beijing Children's Hospital. We also searched Chinese- and English-language databases to identify additional SLS cases for comparative analysis. Structural effects of detected variants on fatty aldehyde dehydrogenase (FALDH) were explored using PDB-derived models and PyMOL.</p><p><strong>Results: </strong>Three SLS patients were identified, including one carrying a novel variant not previously reported. Literature review yielded 19 additional Chinese cases. Globally, SLS has a broad distribution, with the highest case counts reported in the United States, Sweden, and China. Compared with cohorts from other countries, Chinese patients showed a higher proportion of females, and compound heterozygous variants were more frequent than homozygous variants. The c.1157A > G substitution emerged as the most common variant in Chinese SLS. Three-dimensional modeling suggested that several variants likely perturb FALDH conformation.</p><p><strong>Conclusion: </strong>Chinese SLS patients exhibit distinctive clinical and genetic patterns relative to other populations, with c.1157A > G being the most frequent variant. Structural modeling supports a potential conformational impact of these variants on FALDH.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471940","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":"Diagnostic delay, misdiagnosis, and patient-reported psychosocial burden among Chinese individuals with McCune-Albright syndrome: a national cross-sectional survey.","authors":"Ke Yuan, Yilin Zhu, Yonghua Chen, Jianfang Zhu, Yanlan Fang, Chunlin Wang","doi":"10.1186/s13023-026-04507-y","DOIUrl":"10.1186/s13023-026-04507-y","url":null,"abstract":"<p><strong>Background: </strong>McCune-Albright Syndrome (MAS) is a rare, mosaic genetic disorder characterized by fibrous dysplasia of bone, endocrine hyperfunction, and skin pigmentation. Despite increasing clinical recognition, real-world data on diagnostic timelines, disease burden, and psychosocial impact among MAS patients-particularly in China-remain scarce.</p><p><strong>Methods: </strong>We conducted a national, cross-sectional survey of Chinese MAS patients between November 2024 to June 2025 using a structured 95-item online questionnaire disseminated via the McCune-Albright Syndrome Clinical Research Consortium (MASCRC) database and the Bone Care Center patient community. Responses were de-duplicated and managed within the MASCRC data platform. Data were collected on demographics, initial symptoms, diagnostic delay, treatment history, quality of life, psychological distress, and support needs. Descriptive statistics, chi-square tests, and Mann-Whitney U tests were performed.</p><p><strong>Results: </strong>A total of 152 valid responses were analyzed from MAS patients across 28 of 34 provincial-level regions, including 94 females (61.84%) and 58 males (38.16%), with a median age of 10.10 years (IQR: 7.80-15.00). The most common first symptoms were bone involvement (61.18%), peripheral precocious puberty (36.84%), and café-au-lait pigmentation (37.50%). Initial hyperthyroidism and Cushing syndrome were reported in 3.95% and 1.32% of cases, respectively. Median age at symptom onset was 5.50 years; median age at diagnosis was 6.00 years. Although the majority of patients were diagnosed within 1 year (median delay: 0 months, IQR: 0-6), 21.05% experienced a diagnostic delay of ≥ 1 year, and 27.63% reported prior misdiagnosis. GNAS mutation testing was performed in 48.68% of patients, with a detection rate of 36.49%. Long-term consistent treatment was reported by 37.00% of respondents, with regular follow-up (62.50%), medication (38.82%), and surgery (36.18%) being the most common strategies. Impact on daily life was substantial: 46.05% of patients reported moderate to severe disruption in education or employment, and family/economic burden was rated most severe (mean score 3.21/5). Self-reported psychological distress was common, with 78.29% reporting anxiety-related symptoms and 37.50% reporting depressive symptoms, yet only 15.79% accessed professional support. Over 90% expressed unmet needs for expert medical resources, while 79.61% desired improved insurance reimbursement, and 46.05% wished for peer-support platforms.</p><p><strong>Conclusions: </strong>MAS patients in China report substantial clinical and psychosocial burdens, with a subset experiencing prolonged diagnostic journeys and misdiagnoses. These findings highlight a need for earlier recognition, integrated multidisciplinary care, and structured patient support.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456220","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":"Temperature-sensitive auditory neuropathy: long-term follow-up and genotypic correlation.","authors":"Xin Zhou, Qiujing Zhang, Xiaolong Zhang, Xiaonan Wu, Lan Lan, Qiuju Wang","doi":"10.1186/s13023-026-04500-5","DOIUrl":"https://doi.org/10.1186/s13023-026-04500-5","url":null,"abstract":"<p><strong>Background: </strong>Temperature-sensitive auditory neuropathy (TSAN) is a rare disease and a distinctive subtype of auditory neuropathy, characterized by fluctuating hearing thresholds and speech recognition influenced by body or environmental temperature. It is most associated with biallelic variants in the OTOF gene. Despite growing genetic insights, its long-term natural history remains poorly characterized, and the functional consequences of specific OTOF variants are incompletely understood.</p><p><strong>Methods: </strong>This retrospective case series included 5 Han Chinese patients with TSAN carrying OTOF variants. Comprehensive audiological evaluations, including auditory brainstem response (ABR), otoacoustic emissions (OAE), cochlear microphonics (CM), pure-tone audiometry, and speech recognition assessment, were performed. Genetic analyses included whole-exome sequencing, Sanger validation, in silico pathogenicity prediction, and structural modeling. Long-term clinical follow-up ranged from 5 to 21 years.</p><p><strong>Results: </strong>All patients initially presented with mild-to-moderate fluctuating hearing loss, absent ABR, and preserved OAE and/or CM, consistent with AN. Genetic analysis identified 7 rare OTOF variants, including 2 frameshift variants (p. Gln994Valfs*7 and p. Leu795Serfs*5), 1 nonsense variant (p. Arg1134Ter), and 4 missense variants (p. Arg1607Trp, p. Gly541Ser, p. Trp536Cys, and p. Ala1667Asp). Most variants affected evolutionarily conserved residues and were predicted to be deleterious, while structural modeling suggested that the missense variants may alter local protein conformation and stability. Long-term follow-up revealed marked inter-individual variability in auditory outcomes. Several patients achieved near-normal auditory performance without intervention, with Categories of Auditory Performance scores of 7 and Speech Intelligibility Rating scores of 5, whereas others showed persistent speech perception deficits despite only moderate hearing thresholds. Cochlear implantation improved auditory performance in selected patients.</p><p><strong>Conclusions: </strong>OTOF-related TSAN demonstrated substantial clinical heterogeneity but generally favorable long-term functional outcomes in this cohort. These findings contribute to the characterization of the OTOF mutational landscape in TSAN, highlight the importance of long-term monitoring in this rare disease, and support individualized management strategies guided by both genotype and functional auditory performance.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456261","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":"Methodology for eliciting consensus on high-level concepts in rare connective tissue and musculoskeletal diseases (ReCONNET-ELICIT).","authors":"Laurent Arnaud, Guillermo Pons-Estel, Mariele Gatto, Chiara Tani, Hervé Devilliers, Rosaria Talarico, Giuseppe Turchetti, Marta Mosca","doi":"10.1186/s13023-026-04502-3","DOIUrl":"10.1186/s13023-026-04502-3","url":null,"abstract":"<p><p>The ReCONNET-ELICIT methodology represents an innovative and systematic approach to gather expert consensus on complex, high-level concepts related to rare connective tissue and musculoskeletal diseases (rCTDs). Developed within the framework of European Reference Networks (ERNs) ReCONNET, this methodology aims to overcome the challenges associated with defining complex features that lack consensus in rCTDs, such as composite definitions for severe or refractory disease. The core premise of RECONNET-ELICIT is that individual expertise, including that of experts, is inherently limited, but that aggregating insights from a sufficiently large and diverse group can achieve extensive and relevant facet elicitation. The RECONNET-ELICIT process begins with assembling a diverse panel from various geographical backgrounds. This inclusive approach ensures that multiple perspectives are considered. The next step involves crowdsourcing responses through an online survey, where participants suggest as many facets of the high-level concept as possible. These proposals are then systematically analyzed and recoded into broader categories through a consensus-driven binning process. Following this, the panel reviews the consolidated list of facets and votes on their final inclusion, typically utilizing rating scales to minimize bias. This approach is particularly valuable in rCTD contexts where limited data are available. Overall, ReCONNET-ELICIT aim at enhancing the clarity and shared understanding of complex disease concepts by integrating expert insights within an asynchronous, structured, participatory framework while avoiding dominance bias. Its flexibility and focus on collective agreement make it especially useful for advancing knowledge and improving management strategies for rare CTDs.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456215","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":"Burden of respiratory syncytial virus in spinal muscular atrophy: a retrospective nationwide cross-sectional and birth cohort study.","authors":"Hao-Wei Chung, Chen-Hua Wang, Chia-Hung Yu, Chiao-Yun Huang, Fu-Wen Liang","doi":"10.1186/s13023-026-04494-0","DOIUrl":"10.1186/s13023-026-04494-0","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a severe neuromuscular disease associated with a high risk of respiratory complications, yet real-world data on respiratory syncytial virus (RSV) infection in this population remain limited. This study aimed to investigate the severity, hospitalization costs, and seasonal patterns of RSV infections in patients with SMA using real-world data in Taiwan.</p><p><strong>Methods: </strong>This retrospective study analyzed data from Taiwan's National Health Insurance Research Database from 2009 to 2021. Patients with SMA were identified through at least two outpatient clinic visits and one hospital admission. The analysis included a cross-sectional study and a birth cohort analysis for sensitivity testing. RSV-associated hospitalizations were identified using diagnostic codes for RSV. The main outcomes included ICU admissions, ventilator use, hospitalization costs, timing of RSV onset, and seasonal infection trends.</p><p><strong>Results: </strong>This study documented 914 hospitalizations in patients with SMA over 13 years, including 14 RSV infections (1.5%). All RSV-related hospitalizations were documented before age 18. In a birth cohort analysis comparing 110 patients with SMA to 2,103,997 individuals from the general population, patients with SMA demonstrated significantly higher RSV hospitalization rates (9.8% vs. 1.6%), ICU admissions (54.5% vs. 4.7%; p < 0.0001), and ventilator use (54.5% vs. 1.7%; p < 0.0001), with a later mean onset (2.54 ± 2.05 years vs. 1.05 ± 1.05 years; p = 0.0073) and substantially higher hospitalization costs (median 967 [560-6,462] USD vs. 683 [487-1002] USD; p = 0.0480). Infections peaked in fall and winter (72.7%) for patients with SMA. ICU admission rates for RSV increased with age and decreased with later SMA onset.</p><p><strong>Conclusions: </strong>Patients with SMA are at heightened risk for severe RSV infections even beyond infancy, underscoring the need for age-specific and seasonal prevention strategies, particularly for those over two years old.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448712","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, pathological, and genetic characteristics of 23 DMD patients in northern China.","authors":"Yi Bu, Jingzhe Han, Jinliang Deng, Pingping Fang, Di An, Guang Ji, Shaojuan Ma, Xueqin Song","doi":"10.1186/s13023-026-04488-y","DOIUrl":"10.1186/s13023-026-04488-y","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is a rare X-linked neuromuscular disorder characterised by heterogeneous early manifestations. This study summarised the clinical, pathological, and genetic characteristics of patients with DMD in northern China and identified useful indicators for diagnosis and disease assessment.</p><p><strong>Methods: </strong>Twenty-three DMD patients at the Second Hospital of Hebei Medical University between 2014 and 2022 were retrospectively reviewed. Clinical data, laboratory findings, electrocardiography, electromyography, muscle pathology, dystrophin immunohistochemistry, and DMD gene variants were analysed.</p><p><strong>Results: </strong>Age at onset ranged from 0.5 to 7.5 years, mainly between 3.5 and 6.0 years. Bilateral lower-limb weakness and exercise intolerance were observed in 21 patients. All patients had elevated myocardial enzymes, decreased serum creatinine, elevated inorganic phosphate, and myogenic changes on electromyography; 22 had elevated transaminases and 17 had abnormal electrocardiograms. Muscle pathology showed connective tissue and fatty infiltration in all cases, with fibre atrophy. Dystrophin immunohistochemistry revealed complete loss of dystrophin-N/C/R in 21 patients and partial loss in two patients. Muscle strength was positively correlated with CK, CKMB, ALT, AST, LDH, and creatinine. Genetic testing identified 15 deletions, five duplications, and three small mutations, including a novel frameshift variant. Among 21 patients with parental testing, 10 mothers were carriers and 11 cases were considered de novo.</p><p><strong>Conclusions: </strong>DMD exhibited distinct clinicopathological and genetic patterns. Unexplained transaminase or myocardial enzyme elevation, decreased serum creatinine, and early motor abnormalities should prompt DMD genetic testing.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437756","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":"Treating a patient with ADP porphyria through suppression of both hepatic and erythroid ALA production.","authors":"Niels C Veldhoen, Nicole C Peltenburg, Eduard J van Beers, Edith C H Friesema, Janneke G Langendonk","doi":"10.1186/s13023-026-04470-8","DOIUrl":"10.1186/s13023-026-04470-8","url":null,"abstract":"<p><p>δ-Aminolevulinic acid dehydratase deficient porphyria (ADP) is an exceedingly rare form of acute porphyria, with only fifteen published cases worldwide. This disorder has historically been considered an hepatic porphyria, as it was thought the overproduction of the toxic metabolite δ-Aminolevulinic acid (ALA) solely occurred in the liver. This case report demonstrates that treatments focused on reducing the hepatic ALA production had limited effect on this patient's symptoms. An earlier published hypothesis that patients with ADP also produce substantial levels of bone marrow derived ALA, was retested. We describe a Dutch patient in his early 60s, who has suffered from ADP since birth. His medical history mentions acute neurovisceral attacks, contractures of hand and feet, severe polyneuropathy, developmental delay, and renal insufficiency (eGFR 30-40 ml/min). For over a decade he was treated with weekly heme prophylaxis to reduce the frequency of neurovisceral attacks. Despite continuation, his chronic neurological symptoms aggravated and, in an attempt to suppress erythroid ALA production, weekly erythrocyte transfusions combined with hydroxyurea was started. The patient's symptoms improved and stabilized during this treatment. Oral chelation therapy was started to limit secondary iron overload caused by both heme and erythrocyte infusions. Years later we could trial givosiran, an ALAS1-siRNA to suppress the hepatic ALA production. After starting givosiran the heme infusions could be stopped without an increase in symptoms, but discontinuation of erythrocyte transfusions led to new onset neurovisceral attacks. His current schedule consists of continued givosiran and erythrocyte transfusions. This case report illustrates that ADP can be treated successfully with both hepatic and erythroid suppression. It also illustrates the challenges of treating a patient with a rare, complex and poorly understood disease, and the difficulty to balance the complications, side effects and the benefits of treatments.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437744","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}