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Frontometaphyseal dysplasia associated with the FLNA p.G1576R variant 与FLNA p.G1576R变异相关的额干骺端发育不良

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100087

Morten Reiffenstein Huno , Trine Østergaard Nielsen , Michel Bach Hellfritzsch , Sara Markholt , Michael Davidsen , Stine Maria Lund Andersen , Sia Mariann Kjeldsen , Thomas Krusenstjerna-Hafstrøm , Stephen P. Robertson , Pernille Axél Gregersen

{"title":"Frontometaphyseal dysplasia associated with the FLNA p.G1576R variant","authors":"Morten Reiffenstein Huno , Trine Østergaard Nielsen , Michel Bach Hellfritzsch , Sara Markholt , Michael Davidsen , Stine Maria Lund Andersen , Sia Mariann Kjeldsen , Thomas Krusenstjerna-Hafstrøm , Stephen P. Robertson , Pernille Axél Gregersen","doi":"10.1016/j.rare.2025.100087","DOIUrl":"10.1016/j.rare.2025.100087","url":null,"abstract":"<div><div>This report presents a male patient with frontometaphyseal dysplasia (FMD) caused by a previously reported <em>FLNA</em> variant (NM_001456.4:c.4726G>A (p.Gly1576Arg)) that was maternally inherited. This finding directly contrasts with two previously reported observations of the same variant, which led to the suggestion that it is associated with a clinically distinct phenotype. Unlike these earlier descriptions, which did not report either signs of skeletal dysplasia or the typical facial features of FMD, the individual we report here exhibits, supraorbital hyperostosis, a skeletal dysplasia (small femoral epiphyses and bilateral pes cavus), retentio testis, reduced joint mobility, and a congenital cardiac anomaly (Ebstein anomaly). Furthermore, the previous cases documented uric acid renal stones and increased optic cup-to-disc ratio, both of which are not found in this patient. The previously reported individuals also had prominent keloid scarring, that is commonly encountered in individuals with FMD, but notably our patient exhibited hypertrophic scarring. The phenotype we report here suggests a broader phenotypic spectrum associated with this specific <em>FLNA</em> variant than previously recognized, challenging the view that it represents a separate syndrome of cardiac valvulopathy, keloid scarring, and joint mobility reduction and instead suggests it is likely best included within the spectrum of frontometaphyseal dysplasia.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Siblings with Rett Syndrome: A fatal male case and an asymptomatic female carrier 兄弟姐妹患有Rett综合征：一名死亡男性病例和一名无症状女性携带者

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100089

José M. Lazaro-Guevara , Karen M. Garrido-Lopez

{"title":"Siblings with Rett Syndrome: A fatal male case and an asymptomatic female carrier","authors":"José M. Lazaro-Guevara , Karen M. Garrido-Lopez","doi":"10.1016/j.rare.2025.100089","DOIUrl":"10.1016/j.rare.2025.100089","url":null,"abstract":"<div><h3>Background</h3><div>Rett Syndrome (RTT) is an X-linked dominant neurodevelopmental disorder, primarily affecting females. It was previously believed that male cases, although rare, frequently result in severe symptoms and early mortality due to hemizygosity of the X chromosome. However, recent studies show that some males with <em>MECP2</em> variants may present with a broad phenotypic spectrum, including milder forms, as well as a broader spectrum in affected females due to the effect of X-inactivation that previously was underrecognized.</div></div><div><h3>Case presentation</h3><div>We report RTT in two siblings from the same parents, both carrying a pathogenic <em>MECP2</em> mutation (c.763 C>T, p.Arg255*). The male sibling presented early hypotonia, profound developmental delays, and died in infancy. Initially presumed to be a de novo mutation, subsequent expanded genetic testing revealed the mother to be an asymptomatic carrier—likely attributable to favorable or skewed X chromosome inactivation. She had inherited this mutation neither from her father nor her mother, as both maternal grandparents tested negative. Despite two in vitro fertilization (IVF) attempts with preimplantation genetic diagnosis (PGD) in Guatemala (ultimately unsuccessful), the couple conceived naturally. Their female child, who carries the same <em>MECP2</em> mutation, remains asymptomatic at 27 months, demonstrating typical developmental milestones.</div></div><div><h3>Conclusion</h3><div>These findings underscore the broad phenotypic spectrum of RTT, with markedly different clinical outcomes—for this specific case fatal in the hemizygous male and asymptomatic in the female carrier. They also highlight critical considerations for genetic counseling, the financial and emotional challenges inherent in assisted reproductive technologies in resource-limited settings, and the importance of ongoing surveillance for carriers of <em>MECP2</em> mutations due to risk of developing subtle or late-onset features.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Consensus recommendation for the treatment of generalised Myasthenia Gravis with anti-acetylcholine receptor antibodies (gMG AChR+) in Spain 西班牙对抗乙酰胆碱受体抗体（gMG AChR+）治疗广泛性重症肌无力的共识建议

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2024.100051

Elena Cortés-Vicente , Raquel Hernández , Eva Martínez , Julio Pardo , Francisco Javier Rodríguez de Rivera , on behalf of the Neuromuscular Diseases Study Group (GEEN) of the Spanish Society of Neurology

引用次数: 0

Realising the potential impact of artificial intelligence for rare diseases – A framework 实现人工智能对罕见疾病的潜在影响——一个框架

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2024.100057

Tudor Groza , Chun-Hung Chan , David A. Pearce , Gareth Baynam

{"title":"Realising the potential impact of artificial intelligence for rare diseases – A framework","authors":"Tudor Groza , Chun-Hung Chan , David A. Pearce , Gareth Baynam","doi":"10.1016/j.rare.2024.100057","DOIUrl":"10.1016/j.rare.2024.100057","url":null,"abstract":"<div><div>Rare diseases (RD) are conditions affecting fewer than 1 in 2000 persons, with over 7000 largely genetic RDs affecting 3.5 %-5.9 % of the global population, or approximately 262.9–446.2 million people. The substantial healthcare burden and costs, such as the $1 trillion annual expense in the USA, highlight the urgent need for improved RD management. The International Rare Diseases Research Consortium (IRDiRC) addresses this need through global collaboration, aiming for timely and accurate diagnosis, development of 1000 new therapies, and methodologies to measure impact by 2027.</div><div>IRDiRC's initiatives include biannual meetings and workshops, like the AI-focused workshop in October 2023. This identified AI as crucial for advancing RD research and proposed a Framework for AI to enhance the RD patient journey by addressing efficiency and quality of life through modular solutions mapped to critical stages. The Framework integrates diverse data sources to improve diagnosis, treatment, and impact assessment, reflecting a holistic, cross-sector approach. By guiding multi-stakeholder efforts, the Framework aims to harness AI’s potential to significantly improve rare disease care.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C1q deficiency with severe skin manifestations: A case report from Pakistan C1q缺乏伴严重皮肤表现：巴基斯坦1例报告

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100093

Kashmala Hussain , Shamila Ladak , Fizza Akbar , Salman Kirmani , Sadaf Altaf

{"title":"C1q deficiency with severe skin manifestations: A case report from Pakistan","authors":"Kashmala Hussain , Shamila Ladak , Fizza Akbar , Salman Kirmani , Sadaf Altaf","doi":"10.1016/j.rare.2025.100093","DOIUrl":"10.1016/j.rare.2025.100093","url":null,"abstract":"<div><h3>Background</h3><div>C1q deficiency is a rare autosomal recessive disorder associated with increased susceptibility to infections and autoimmune diseases, notably systemic lupus erythematosus (SLE). Due to its rarity and varied presentation, there are no established guidelines for management. Due to highly variable clinical symptomatology, standard treatment approaches are lacking.</div></div><div><h3>Case presentation</h3><div>We report the case of an 11-month-old Pakistani girl presenting with a desquamating rash and recurrent infections. Initial management with multiple antibiotics and antifungals was ineffective. Upon admission to our facility, clinical and laboratory evaluations indicated severe immunodeficiency. Whole exome sequencing (WES) identified a novel homozygous likely pathogenic variant in the <em>C1qA</em> (c..474C > G, p.Tyr158*), leading to C1q deficiency. Treatment included corticosteroids, antibiotics, and fresh frozen plasma (FFP) transfusions, resulting in clinical improvement.</div></div><div><h3>Discussion</h3><div>C1q deficiency, though rare, presents with diverse clinical manifestations, primarily cutaneous and infectious. Early genetic diagnosis is essential for appropriate management. This case underscores the potential role of FFP in treating C1q deficiency, though more research is needed on its efficacy and safety.</div></div><div><h3>Conclusion</h3><div>This case emphasizes the importance of recognizing C1q deficiency in patients suspected of an underlying immunodeficiency syndrome. Clinical response to FFP infusions suggests that these patients if identified early can have control of symptoms. Early molecular diagnosis through genetic testing and tailored therapeutic approaches are crucial for improving outcomes in these patients. Further research into targeted therapies and the broader implications of C1q in health and disease is essential.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel homozygous stop-gain variant in LRRC32 causing cleft palate, proliferative retinopathy, and developmental delay 一种新的纯合子LRRC32停止增益变异导致腭裂，增殖性视网膜病变和发育迟缓

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100101

Sameeta Kumari , Fizza Akbar , Seung Woo Ryu , Arshalooz Rahman , Salman Kirmani

引用次数: 0

Methodological considerations and implications for appetite and feeding behaviour research in PKU; Current knowledge, practical application and future perspectives 北大鼠食欲与摄食行为研究的方法学思考与启示当前知识、实际应用和未来展望

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100060

Ben Green

{"title":"Methodological considerations and implications for appetite and feeding behaviour research in PKU; Current knowledge, practical application and future perspectives","authors":"Ben Green","doi":"10.1016/j.rare.2025.100060","DOIUrl":"10.1016/j.rare.2025.100060","url":null,"abstract":"<div><div>Appetite and the regulation of feeding behaviour are sophisticated processes. Regulated through homeostatic and non-homeostatic influences, appetite-related peptides and external cues existing in the physical environment work synergistically to maintain energy homeostasis. Phenylketonuria (PKU) is a rare disorder impacting phenylalanine metabolism. The disrupted breakdown of phenylalanine into tyrosine and its metabolites may impact the mechanisms controlling appetite and feeding behaviour compared to non-PKU counterparts. This may, in part, relate to consumption of L-amino acid protein substitutes and specialist low-protein foods which are integral adjuncts to the dietary management of PKU. While adequate energy intake is an important factor for maintaining satisfactory blood phenylalanine concentrations, appetite and feeding behaviour should, therefore, represent an integral consideration for PKU but is currently understudied. Only a handful of studies have evaluated appetite and feeding behaviour in PKU. The most appropriate methodological approaches of these studies however were not employed. This manuscript, therefore, reviews the purported mechanisms controlling appetite and feeding behaviour and from a PKU perspective provides readers with sound study design proposals and justification. Though one method will not answer all research questions, this manuscript may help researchers and practitioners make informed decisions about what tools and methodological approaches will provide the most meaningful outcomes. The manuscript concludes with suggestions for future research directions. Though the evidence concerning appetite and feeding behaviour in PKU remains equivocal at present, early data appears to indicate that protein substitutes with glycomacropeptide facilitate metabolic control and improve appetite-relate peptide regulation and therefore satiety signalling in PKU.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Case reports of the 13th Undiagnosed Diseases Network International Conference 5-7 September 2024 – Seoul, Korea 2024年9月5日至7日在韩国首尔举行的第13届未确诊疾病网络国际会议病例报告

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100084

引用次数: 0

“True Faces of Rare”: Preferences for authentic imagery in disorder-specific materials by people living with rare diseases and their communities “罕见的真实面孔”：罕见疾病患者及其社区对特定疾病材料中真实图像的偏好

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100070

Laura Smith van Carroll , Pavel Krepelka , Kirsty Hoyle , Kamran Iqbal , Tom Kenny

{"title":"“True Faces of Rare”: Preferences for authentic imagery in disorder-specific materials by people living with rare diseases and their communities","authors":"Laura Smith van Carroll , Pavel Krepelka , Kirsty Hoyle , Kamran Iqbal , Tom Kenny","doi":"10.1016/j.rare.2025.100070","DOIUrl":"10.1016/j.rare.2025.100070","url":null,"abstract":"<div><div>This study explores the preferences of people living with rare diseases and their communities regarding the use of authentic imagery in disorder-specific materials. Through a digital survey of 50 respondents, we examined the perceived importance of using images of people affected by a rare disorder in educational and awareness materials about their specific disorder. Results reveal a strong preference for authentic imagery, with most respondents rating this as highly important. People living with rare diseases expressed that seeing “real faces” of those with the condition fosters a sense of connection, combats isolation, and raises public awareness through greater exposure. Conversely, some respondents noted the risk of stereotyping based on appearance, indicating the need for sensitive, accurate portrayal. Our findings suggest that authentic imagery can improve engagement and create an emotional connection with materials, by those living with rare diseases and their communities. Furthermore, we provide actionable recommendations for developers of these materials including patient advocacy groups, research institutions and pharmaceutical companies.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incidental findings in surveillence of paediatric Li Fraumeni patients – A single centre experience 在监测儿科李弗鲁梅尼患者的偶然发现-单一中心的经验

Rare Pub Date : 2025-01-01 DOI: 10.1016/j.rare.2025.100067

Amy Alcock , Elizabeth McVittie , Zoe Nicholls , Hector Conti , Mark Davies , Rhian Isaac , Madeleine Adams , on behalf of the All Wales Paediatric Cancer Predisposition Service

引用次数: 0