Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides–Baraitser Syndrome (SMARCA2 Mutation)—Due to a POLG1-Related Effect?

2019 ◽  
Vol 51 (01) ◽  
pp. 049-052
Author(s):  
Benedikt Hofmeister ◽  
Celina von Stülpnagel ◽  
Steffen Berweck ◽  
Angela Abicht ◽  
Gerhard Kluger ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Literature Review ◽  
Rare Disease ◽  
Clinical Features ◽  
Rare Diseases ◽  
Rare Complication ◽  
Genetic Diseases ◽  
Related Effect ◽  
Higher Sensitivity ◽  
Polg1 Mutation

AbstractNicolaides–Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.

scholarly journals Research and Management of Rare Diseases in the COVID-19 Pandemic Era: Challenges and Countermeasures

2021 ◽  
Vol 9 ◽  
Author(s):  
Sanjana Fatema Chowdhury ◽  
Syed Muktadir Al Sium ◽  
Saeed Anwar
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Management Strategies ◽  
Routine Care ◽  
Ongoing Research ◽  
The People ◽  
Number Of Patients ◽  
High Level ◽  
Disease Community

The ongoing coronavirus disease 2019 (COVID-19) pandemic has disrupted every aspect of our life. The need to provide high-level care for an enormous number of patients with COVID-19 infection during this pandemic has impacted resourcing for and restricted the routine care of all non-COVID-19 conditions. Since the beginning of the pandemic, the people living with rare disorders, who represent a marginalized group of the population even in a normal world, have not received enough attention that they deserve. Due to the pandemic situation, they have experienced (and experiencing) an extreme inadequacy of regular clinical services, counseling, and therapies they need, which have made their life more vulnerable and feel more marginalized. Besides, the clinicians, researchers, and scientists working on rare genetic diseases face extra challenges due to the pandemic. Many ongoing research projects and clinical trials for rare and genetic diseases were stalled to avoid patients' and research staff's transmission to COVID-19. Still, with all the odds, telehealth and virtual consultations for rare disease patients have shown hope. The clinical, organizational, and economic challenges faced by institutions, patients, their families, and the caregivers during the pandemic indicate the importance of ensuring continuity of care in managing rare diseases, including adequate diagnostics and priority management strategies for emergencies. In this review, we endeavored to shed light on the issues the rare disease community faces during the pandemic and the adaptations that could help the rare disease community to better sustain in the coming days.

scholarly journals RDmap: A Map for Exploring Rare Diseases

2021 ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results: A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3,287 rare diseases are included in the phenotype-based map, and 3,789 rare genetic diseases are included in the gene-based map; 1,718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals Genomics of rare genetic diseases—experiences from India

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Sridhar Sivasubbu ◽  
◽  
Vinod Scaria
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Collaborative Research ◽  
Disease Burden ◽  
Genetic Diseases ◽  
Community Services ◽  
Health Concern ◽  
Healthy Population ◽  
Rare Genetic Diseases ◽  
Research Initiative

Abstract Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India. Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma. In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India.

PP154 Funding Of Treatments For Rare Diseases In Singapore

2020 ◽  
Vol 36 (S1) ◽  
pp. 17-18
Author(s):  
Fiona Pearce ◽  
Liang Lin ◽  
Kwong Ng
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Evaluation Process ◽  
Public Healthcare ◽  
Clinical Group ◽  
Eligibility Criteria ◽  
Number Of Patients ◽  
Emerging Treatments ◽  
Multi Stakeholder

IntroductionA national multi-stakeholder charity fund has been established in Singapore to provide targeted support to patients with rare genetic diseases whose treatment costs remain unaffordable despite government subsidies and insurance. This presentation will provide an overview of the evaluation, price-setting, and stakeholder engagement processes established to inform the first list of drugs eligible for funding under the Rare Disease Fund (RDF).MethodsThe local prevalence of “rare” and “ultra-rare” conditions was defined in line with international rates (≤4 in 10,000 and <2 in 50,000, respectively) to facilitate an analysis of the rare disease landscape in Singapore, and to identify patients most likely to benefit from the RDF. Public healthcare institutions proposed drugs for consideration, which underwent technical evaluation and were then assessed in line with eligibility criteria by an expert clinical group and prioritized by decision makers for funding.ResultsThe number of patients with select rare diseases in Singapore was lower than global estimates contextualized to the local setting. Supporting clinical evidence, funding decisions from overseas health technology assessment agencies, reference pricing considerations, and local budget impact analyses informed the first tranche of drugs (n = 5) recommended. Extensive engagement with pharmaceutical companies was needed to negotiate fair drug prices relative to overseas countries. Additional treatments will be included in the RDF once sufficient funds are raised.ConclusionsAs the evaluation process evolves, wider considerations of disease and treatment experiences from a multi-stakeholder standpoint should be included to inform RDF listings. There is also a need to balance the sustainability of the fund in the longer term with the number of emerging treatments that may require coverage in the future.

scholarly journals RDmap: a map for exploring rare diseases

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Disease Diagnosis ◽  
Human Phenotype ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map

Abstract Background The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts. Results A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3287 rare diseases are included in the phenotype-based map, and 3789 rare genetic diseases are included in the gene-based map; 1718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis. Conclusion RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.

scholarly journals RDmap: A Map for Exploring Rare Diseases

2020 ◽  
Author(s):  
Jian Yang ◽  
Cong Dong ◽  
Huilong Duan ◽  
Qiang Shu ◽  
Haomin Li
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Keyword Search ◽  
Genetic Diseases ◽  
Distance Matrix ◽  
Pathogenic Genes ◽  
Disease Information ◽  
Rare Genetic Diseases ◽  
Interactive Map ◽  
Location Function

Abstract Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases make the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: By defining the quantitative distance among phenotypes and pathogenic genes based on corresponding ontology systems, the distance matrix of rare diseases included in Orphanet was calculated and mapped into Euclidean space. Enhanced by clustering classes and disease information, a rare disease map was developed based on ECharts. Results: The rare disease map called RDmap was published at http://rdmap.nbscn.org. The phenotype-based map comprises 3,287 rare diseases and the gene-based map comprises 3,789 rare genetic diseases and they were bridged by 1,718 overlapping diseases. RDmap works similar to the widely used Google map and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword search in an in-silico evaluation and 20 published cases of rare diseases also demonstrated that RDmap can be used by clinicians to improve diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasing complicated rare genetic diseases.

scholarly journals Perceptions and experiences of rare diseases among the GP population in Northern Ireland

2019 ◽  
Vol 69 (suppl 1) ◽  
pp. bjgp19X703637
Author(s):  
Julie McMullan ◽  
Taylor McC lenaghan ◽  
Ashleen Crowe ◽  
Amy Jayne McKnight ◽  
Helen McAneney
Keyword(s):  
Northern Ireland ◽  
Literature Review ◽  
Rare Disease ◽  
Rare Diseases ◽  
Information Needs ◽  
Online Survey ◽  
Qualitative Interviews ◽  
Genomic Medicine ◽  
Healthcare Delivery ◽  
Depth Information

BackgroundRare diseases are often complex, life-long conditions with a genetic basis. With advances in phenotyping and genomic medicine, there are now >8000 rare diseases reported. A rare disease is defined by an incidence of <5 cases per 10 000 population; although they are individually rare, collectively they are much more common with 1 in 17 persons affected in their lifetime. The Northern Ireland Rare Disease Implementation Plan (2015) highlighted the need for better coordination of care, the empowerment of patients, better diagnostics, and earlier disease interventions. The report also acknowledged the difficult role that GPs have, especially in the diagnosis of rare diseases. GPs play an important role in healthcare delivery for people living with a rare disease and their families. However, many GPs report challenge identifying and managing individuals with a rare disease appropriately.AimTo explore GP’s perceptions and experiences of rare diseases.MethodA literature review of published research related to GPs and rare disease will be conducted. Databases searched include Medline, Embase, Web of Science, Scopus and Google Scholar. Additionally, an online survey will be completed by GPs November 2018–spring 2019, with follow-up qualitative interviews providing further in-depth information.ResultsInitial searches have revealed 27 relevant publications. A summary of the findings from the literature review will be presented, alongside findings from our GP survey.ConclusionMuch can be learned from the experiences of current GPs to identify rare disease information needs and resources that enable effective GP-patient partnerships.

scholarly journals Network analysis reveals rare disease signatures across multiple levels of biological organization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pisanu Buphamalai ◽  
Tomislav Kokotovic ◽  
Vanja Nagy ◽  
Jörg Menche
Keyword(s):  
Rare Disease ◽  
Rare Diseases ◽  
Single Gene ◽  
Genetic Diseases ◽  
Physical Interaction ◽  
Biological Organization ◽  
Network Layers ◽  
Disease Module ◽  
Gene Defects ◽  
The Impact

AbstractRare genetic diseases are typically caused by a single gene defect. Despite this clear causal relationship between genotype and phenotype, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, we introduce a network approach for evaluating the impact of rare gene defects across biological scales. We construct a multiplex network consisting of over 20 million gene relationships that are organized into 46 network layers spanning six major biological scales between genotype and phenotype. A comprehensive analysis of 3,771 rare diseases reveals distinct phenotypic modules within individual layers. These modules can be exploited to mechanistically dissect the impact of gene defects and accurately predict rare disease gene candidates. Our results show that the disease module formalism can be applied to rare diseases and generalized beyond physical interaction networks. These findings open up new venues to apply network-based tools for cross-scale data integration.

scholarly journals Case report and literature review: Horner syndrome subsequent to endoscopic thyroid surgery

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Min ◽  
Hang Chen ◽  
Xing Wang ◽  
Ying Huang ◽  
Guobing Yin
Keyword(s):  
Literature Review ◽  
Thyroid Surgery ◽  
Thyroid Nodules ◽  
Rare Complication ◽  
Needle Aspiration ◽  
Horner Syndrome ◽  
Central Lymph Node Dissection ◽  
Thyroid Microcarcinoma ◽  
Endoscopic Thyroid Surgery ◽  
Central Lymph

Abstract Background Horner syndrome (HS), mainly characterized by symptoms including ptosis, miosis, and anhidrosis on the affected face, is a condition that is well documented but rarely reported as a postoperative complication of thyroidectomy, particularly in endoscopic thyroid surgery (ETS). We hereby report a case of HS due to ETS with a brief literature review on this topic. Case presentation A 31-year-old female was admitted to our hospital with an unexpected physical examination finding of two thyroid nodules that were hypoechoic, had an irregular shape, and exhibited calcification. Subsequently, the results of a fine-needle aspiration (FNA) biopsy from the thyroid nodules and BRAFV600E mutation further confirmed the malignancy of these nodules. Thus, total thyroidectomy combined with central lymph node dissection (CLND) by ETS via the bilateral axillo-breast approach was performed on this patient. Histology confirmed the diagnosis of papillary thyroid microcarcinoma (PTMC) concurrent with Hashimoto’s thyroiditis (HT). However, this patient developed HS with ptosis in her left eye on postoperative day 3. All symptoms gradually resolved before the 3-month follow-up. Conclusion HS subsequent to ETS is a rare complication. Thus, standardized and appropriate operative procedures, as well as subtle manipulation, are essential in preventing and reducing the occurrence of HS. In addition, the early diagnosis and management of this rare complication are also important for a favorable outcome.

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