Translational science of rare diseases最新文献

{"title":"The Rare Disease Research Scholars Program: A training curriculum for clinical researchers with mixed methods evaluation study","authors":"D. Regier, Jennifer A. Weaver, Nancy Cheng, M. Batshaw, M. Ottolini, M. Shy, M. Summar","doi":"10.3233/TRD-210051","DOIUrl":"https://doi.org/10.3233/TRD-210051","url":null,"abstract":"Rare disease clinician investigators are essential to ensure appropriate diagnosis, care, and treatment for the rapidly growing rare disease population. As these researchers are spread across many specialties, learning the unique skill set for rare disease research (RDR) can be a hurdle and may hinder progress in the field. The need for an RDR focused training program for investigators in many specialties and backgrounds was identified in a needs assessment of trainees in the NIH funded Rare Diseases Clinical Research Network. Based on this information, the Rare Disease Research Scholars Program (RDRSP) was developed. We describe the needs assessment, curriculum creation, scholar recruitment, and outcome evaluation based on four years of programmatic data (2015–2019). This one year-long RDRSP uses a blended approach that includes in-person, web-based, synchronous and asynchronous learning. We evaluated the RDRSP using quantitative and qualitative approaches. Quantitative measures included pre and post questionnaires about knowledge, self-efficacy, and intent to remain in RDR. Data were analyzed using descriptive statistics and a paired t-test. Qualitative semi-structured interviews explored the RDR scholars’ perceptions of the RDRSP; thematic analysis examined the textual data. Quantitative pre- and post-measures were statistically significant in the following areas: 1) improved knowledge content in RDR, 2) enhanced self-efficacy in clinical research, and 3) intent to remain in the field of RDR. Qualitative data analysis found the program supported the development of the scholar’s research skills as well as ‘soft-skills’. By combining training of skills unique to RDR with the more general topics of leadership, mentorship and collaboration among participants in diverse specialties, we created a program that supports the development of the next generation of rare disease clinician investigators and serves as a model for training in other niche research areas.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"6 1","pages":"1 - 11"},"PeriodicalIF":0.0,"publicationDate":"2021-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42052037","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}

{"title":"Report of the 2021 Primary ciliary dyskinesia foundation annual meeting","authors":"Thomas G. Saba, S. Brody","doi":"10.3233/trd-210052","DOIUrl":"https://doi.org/10.3233/trd-210052","url":null,"abstract":"In August 2021, the Primary Ciliary Dyskinesia (PCD) Foundation hosted a 2-day international virtual conference designed to share discoveries in PCD genetics, cilia biology, and clinical research and care. The conference was organized around the theme of building a community for clinical research. This article provides a report of the proceedings.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45323455","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}

{"title":"Efficacy and safety of long-term sirolimus use as part of multidisciplinary care in a pediatric patient with CLOVES syndrome: Case report","authors":"Alexis Leonard, Yaser A Diab, L. Tosi","doi":"10.3233/TRD-200050","DOIUrl":"https://doi.org/10.3233/TRD-200050","url":null,"abstract":"BACKGROUND: CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal/spinal) syndrome is a rare and progressive genetic disorder resulting from somatic mosaicism in activating mutations in the phosphatidylinositol-4,5- bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. PIK3CA is a cell growth master regulator where gain of function mutations give rise to abnormal activation of the PI3K-AKT- mammalian target of rapamycin (mTOR) pathway. Treatment with sirolimus, an mTOR inhibitor, may therefore be of benefit in patients with CLOVES syndrome. OBJECTIVE: Here we describe the efficacy and toxicity of sirolimus in a pediatric patient with progressive CLOVES syndrome. RESULTS: The child presented with a large and painful abdominal malformation, massive overgrowth of his feet, limb length discrepancy and genu valgum. There was dramatic clinical and radiographic improvement in the size and comfort of his abdominal mass within several months of initiating medical therapy. This, combined with orthopaedic care of his genu valgum, leg length discrepancy, and overgrowth of his feet, has allowed for significant functional gains. CONCLUSIONS: Multidisciplinary care is essential for comfort and functional gains in patients with CLOVES syndrome, particularly those with severe symptoms. Close monitoring while on sirolimus medical therapy combined with frequent reassessment of orthopedic needs can dramatically improve patient quality of life and outcomes.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/TRD-200050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42875144","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}

{"title":"Rett syndrome: Novel correlations linking >96% genotype, disease severity, and seizures","authors":"L. M. Rodriguez, A. Percy, G. Cutter","doi":"10.3233/trd-200047","DOIUrl":"https://doi.org/10.3233/trd-200047","url":null,"abstract":"BACKGROUND: Rett Syndrome (RTT), an incurable neurodevelopmental disorder associated in >96% with the X-linked gene, MECP2 includes seizures, among its most difficult issues, impacting many features and increasing morbidity and mortality. Linking these seizures with clinical severity in RTT is critical for estimating risk and guiding therapy. OBJECTIVE: Our primary purpose was to identify associations between type and frequency of seizures, disease severity, and specific MECP2 mutations to address the hypothesis that seizure frequency correlates with specific mutations and directly impacts clinical severity. METHODS: Mutation, seizure type and frequency, and clinical severity assessed by the Clinical Severity Scale (CSS) were extracted from the 5211 Natural History Study of Rett Syndrome and Related Disorders [1]. This involved observations from 222 Persons with classic or variant RTT and MECP2 mutation positive non-Rett diagnoses. Descriptive analyses were assessed utilizing SPSS software. Mutations include R106W, R133C, R168X, R294X, R306C, other point mutations, and early truncations. RESULTS: Greater frequency of generalized seizures and seizures of any type were associated with R106W mutations; R168X mutations had the highest disease severity, and R133C mutations had the lowest disease severity. CONCLUSION: Important correlations exist across several common MECP2 mutations, including the novel association between generalized seizure frequency and mild CSS.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/trd-200047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47072047","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}

{"title":"Opportunities, barriers, and recommendations in down syndrome research.","authors":"James A Hendrix, Angelika Amon, Leonard Abbeduto, Stamatis Agiovlasitis, Tarek Alsaied, Heather A Anderson, Lisa J Bain, Nicole Baumer, Anita Bhattacharyya, Dusan Bogunovic, Kelly N Botteron, George Capone, Priya Chandan, Isabelle Chase, Brian Chicoine, Cécile Cieuta-Walti, Lara R DeRuisseau, Sophie Durand, Anna Esbensen, Juan Fortea, Sandra Giménez, Ann-Charlotte Granholm, Laura J Hahn, Elizabeth Head, Hampus Hillerstrom, Lisa M Jacola, Matthew P Janicki, Joan M Jasien, Angela R Kamer, Raymond D Kent, Bernard Khor, Jeanne B Lawrence, Catherine Lemonnier, Amy Feldman Lewanda, William Mobley, Paul E Moore, Linda Pollak Nelson, Nicolas M Oreskovic, Ricardo S Osorio, David Patterson, Sonja A Rasmussen, Roger H Reeves, Nancy Roizen, Stephanie Santoro, Stephanie L Sherman, Nasreen Talib, Ignacio E Tapia, Kyle M Walsh, Steven F Warren, A Nicole White, Guang William Wong, John S Yi","doi":"10.3233/trd-200090","DOIUrl":"10.3233/trd-200090","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community.</p><p><strong>Objective: </strong>The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan.</p><p><strong>Methods: </strong>NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS.</p><p><strong>Results: </strong>This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade.</p><p><strong>Conclusions: </strong>This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.</p>","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"5 3-4","pages":"99-129"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/14/nihms-1693350.PMC8279178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9757024","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}

{"title":"Disorders of phenylalanine and tyrosine metabolism","authors":"H. Alsharhan, C. Ficicioglu","doi":"10.3233/trd-200049","DOIUrl":"https://doi.org/10.3233/trd-200049","url":null,"abstract":"This article provides a review of the inborn errors of phenylalanine and tyrosine metabolism including the diagnostic approach, dietary and pharmalogical management and emerging therapies. Hyperphenylalaninaemia results mainly from defects in either phenylalanine hydroxylase (PAH) (resulting in phenylketonuria (PKU)) or the production or recycling of tetrahydrobiopterin (BH4). Untreated PKU results in irreversible neurocognitive impairment. Five inherited disorders of tyrosine metabolism are known, which include tyrosinemia type I, type II, type III, hawkinsinuria and alkaptonuria. Newborn screening for these disorders has enabled their early detection and decreased the associated morbidity and mortality.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/trd-200049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49139225","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}

{"title":"Multimodal imaging in urea cycle-related neurological disease - What can imaging after hyperammonemia teach us?","authors":"Kuntal Sen,&nbsp;Matthew T Whitehead,&nbsp;Andrea L Gropman","doi":"10.3233/TRD-200048","DOIUrl":"https://doi.org/10.3233/TRD-200048","url":null,"abstract":"<p><strong>Background: </strong>Urea cycle-related brain disease may take on variable neuroimaging manifestations, ranging from normal to abnormal with or without a signature appearance. In the past, we have described the usefulness of multimodal imaging in identifying biomarkers of neuronal injury in UCD patients. In this study, we report unique findings in an adolescent male with neonatal-onset OTC deficiency after an episode of hyperammonemia.</p><p><strong>Materials and methods: </strong>Multiplanar, multisequence MR imaging (T1WI, T2WI, T2 FLAIR, diffusion weighted images and gradient echo) of the brain was performed on seven separate occasions over the course following the acute illness; first five exams were performed within 28 days of admission and the final two exams were performed approximately 3 and 5 months later.</p><p><strong>Results: </strong>1.The initial MR revealed increased signal on T2WI in the basal ganglia, claustrum and frontoparietal white matter; which remained stable over time. By the 5th exam, signal changes had developed in frontal cortex; reflecting permanent injury. 2. DTI tractography of the corticospinal tracts displayed revealed diminution of the number of projectional and commissural fibers over time. 3. Blood flow measurements demonstrated hypoperfusion on the fifth exams followed by hyperperfusion on the final two studies. 4. MR spectroscopy demonstrated that glutamine was elevated during hyperammonemia with myoinositol reduction, reflecting osmotic buffering.</p><p><strong>Conclusion: </strong>This particular multimodal magnetic resonance neuroimaging showed novel, temporally specific manifestations over the disease course in OTC deficiency. This prospective imaging study expands our understanding of the effect of hyperammonemia on the structure and biochemistry of the nervous system.</p>","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"5 1-2","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/TRD-200048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38733526","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}

{"title":"Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis.","authors":"Firas Alqarajeh,&nbsp;Jacklyn Omorodion,&nbsp;Kerri Bosfield,&nbsp;Natasha Shur,&nbsp;Carlos R Ferreira","doi":"10.3233/TRD-190035","DOIUrl":"https://doi.org/10.3233/TRD-190035","url":null,"abstract":"<p><strong>Background: </strong>Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder characterized by deficient membrane transport of cationic amino acids. It is caused by pathogenic variants in SLC7A7, resulting in impairment of intestinal import and renal proximal tubule loss of the affected amino acids. LPI typically presents with gastrointestinal symptoms, such as vomiting, diarrhea, and failure to thrive.</p><p><strong>Case report: </strong>A 4-year-old African-American boy presented with multiple respiratory tract infections, weight loss in the setting of chronic diarrhea and worsening abdominal distention, and multiple episodes of rectal prolapse. Development was unaffected. Laboratory examination demonstrated mild anemia, hypokalemia and hypoalbuminemia, transaminitis, and normal ammonia. Initial urine amino acid analysis did not show major elevations of lysine and ornithine, often lower than expected in the setting of malnutrition. Upon initiation of total parenteral nutrition (TPN), his urine amino acids showed a characteristic profile of dibasic aminoaciduria.</p><p><strong>Conclusions: </strong>Failure to thrive, chronic diarrhea, and hepatomegaly should raise suspicion for LPI. Urine amino acids can be normal in this condition in the setting of malnutrition, a common complication of the disease. Additionally, it has been previously shown that the plasma arginine and ornithine concentration is higher in LPI subjects.</p>","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"5 1-2","pages":"81-86"},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/TRD-190035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38554844","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}

{"title":"Management of rare diseases","authors":"","doi":"10.3233/trd-200001","DOIUrl":"https://doi.org/10.3233/trd-200001","url":null,"abstract":"","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/trd-200001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43137877","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}

{"title":"Practical recommendations for the transition to adulthood for the adolescent with a genetic diagnosis. Special emphasis on inborn errors of metabolism","authors":"M. D. Castro, C. Turner, B. Kirmse","doi":"10.3233/trd-190042","DOIUrl":"https://doi.org/10.3233/trd-190042","url":null,"abstract":". Taken as a group, genetic disorders affect a significant proportion of the population. Historically thought of as pediatric disorders, inborn errors of metabolism (IEM) are becoming increasingly relevant to the adult clinical provider; given the improvements in screening, diagnosis and management, an increasing number of children with IEM’s are able to transition adulthood. Currently available data suggests that adult-medicine clinical providers are ill-prepared to appropriately care for this population. Although practical management and transition guidelines exist for a minority of disorders, there is a significant lack of guidance for the great majority of conditions. Based on our review of the relevant literature, we set out to provide practical recommendations to assist in the transition from adolescence to adulthood, with an emphasis on patients with an inborn error of metabolism.","PeriodicalId":75246,"journal":{"name":"Translational science of rare diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/trd-190042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69508858","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}