scholarly journals Understanding Barriers to Diagnosis in a Rare, Genetic Disease: Delays and Errors Diagnosing Schwannomatosis

2022 ◽  
Author(s):  
Vanessa L Merker ◽  
Bronwyn Slobogean ◽  
Justin L Jordan ◽  
Shannon Langmead ◽  
Mark Meterko ◽  
...  
Keyword(s):  
Median Time ◽  
Tumor Imaging ◽  
Genetic Diseases ◽  
Tertiary Care ◽  
Diagnostic Process ◽  
Expert Review ◽  
Rare Genetic Diseases ◽  
Diagnostic Framework ◽  
Neurogenetic Syndrome ◽  
Diagnostic Delays

Diagnosis of rare, genetic diseases is challenging, but conceptual frameworks of the diagnostic process can be used to guide benchmarking and process improvement initiatives. Using the National Academy of Medicine diagnostic framework, we assessed the extent of, and reasons for, diagnostic delays and errors in schwannomatosis, a neurogenetic syndrome characterized by nerve sheath tumors and chronic pain. We reviewed the medical records of 97 patients with confirmed or probable schwannomatosis seen in two U.S. tertiary care clinics from 2005-2016. Survival analysis revealed a median time from first symptom to diagnosis of 16.7 years (95% CI, 7.5-26.0 years) and median time from first medical consultation to diagnosis of 9.8 years (95% CI, 3.5-16.2 years). Factors associated with longer times to diagnosis included initial signs/symptoms that were intermittent, non-specific, or occurred at younger ages (p<0.05). Thirty-six percent of patients experienced a misdiagnosis of underlying genetic condition (18.6%), pain etiology (16.5%) and/or tumor imaging/pathology (11.3%). One-fifth (19.6%) of patients had a clear missed opportunity for appropriate workup that could have led to an earlier schwannomatosis diagnosis. These results suggest that interventions in clinician education, genetic testing availability, expert review of pathology findings, and automatic triggers for genetics referrals may improve diagnosis in schwannomatosis.

Whole-genome sequencing as a first-tier diagnostic framework for rare genetic diseases

2021 ◽  
pp. 153537022110400
Author(s):  
Haseeb Nisar ◽  
Bilal Wajid ◽  
Samiah Shahid ◽  
Faria Anwar ◽  
Imran Wajid ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genetic Diseases ◽  
Correct Diagnosis ◽  
Clinical Settings ◽  
Whole Genome ◽  
Rare Genetic Diseases ◽  
Diagnostic Approaches ◽  
Diagnostic Framework

Rare diseases affect nearly 300 million people globally with most patients aged five or less. Traditional diagnostic approaches have provided much of the diagnosis; however, there are limitations. For instance, simply inadequate and untimely diagnosis adversely affects both the patient and their families. This review advocates the use of whole genome sequencing in clinical settings for diagnosis of rare genetic diseases by showcasing five case studies. These examples specifically describe the utilization of whole genome sequencing, which helped in providing relief to patients via correct diagnosis followed by use of precision medicine.

scholarly journals Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond

2021 ◽  
Vol 18 (16) ◽  
pp. 8242
Author(s):  
Michał Nowicki ◽  
Stanisława Bazan-Socha ◽  
Mariusz Kłopotowski ◽  
Beata Błażejewska-Hyżorek ◽  
Mariusz Kusztal ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Genetic Diseases ◽  
Healthcare Providers ◽  
Treatment Programs ◽  
Current Therapy ◽  
Term Care ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Home Based ◽  
Rare Genetic Diseases

Current therapy for Anderson–Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020–2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson–Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson–Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

scholarly journals High-Throughput Sequencing and Rare Genetic Diseases

2012 ◽  
Vol 3 (5) ◽  
pp. 197-203 ◽  
Author(s):  
P. Makrythanasis ◽  
S.E. Antonarakis
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Genetic Diseases ◽  
Rare Genetic Diseases

Burden of care in families of patients with rare genetic diseases: analysis of a large Italian cohort

2021 ◽  
pp. 104230
Author(s):  
Alex Moretti ◽  
Paola Cianci ◽  
Anita De Paoli ◽  
Francesca Meroni ◽  
Silvia Tajè ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Burden Of Care ◽  
Rare Genetic Diseases ◽  
Italian Cohort

Ethics and equity in rare disease research and healthcare

2021 ◽  
Author(s):  
Maria Koromina ◽  
Vasileios Fanaras ◽  
Gareth Baynam ◽  
Christina Mitropoulou ◽  
George P Patrinos
Keyword(s):  
Rare Diseases ◽  
Ethical Issues ◽  
Genetic Diseases ◽  
Ethical Framework ◽  
Middle Income ◽  
Next Generation Sequencing Technology ◽  
Ethical Frameworks ◽  
Rare Genetic Diseases ◽  
Conducting Research ◽  
Key Aspects

Rapid advances in next-generation sequencing technology, particularly whole exome sequencing and whole genome sequencing, have greatly affected our understanding of genetic variation underlying rare genetic diseases. Herein, we describe ethical principles of guiding consent and sharing of genomics research data. We also discuss ethical dilemmas in rare diseases research and patient recruitment policies and address bioethical and societal aspects influencing the ethical framework for genetic testing. Moreover, we focus on addressing ethical issues surrounding research in low- and middle-income countries. Overall, this perspective aims to address key aspects and issues for building proper ethical frameworks, when conducting research involving genomics data with a particular emphasis on rare diseases and genetics testing.

scholarly journals Outcomes of Percutaneous Tracheostomy for Patients with SARS-CoV-2 Respiratory Failure

2021 ◽  
Author(s):  
Jason Arnold ◽  
Catherine A. Gao ◽  
Elizabeth Malsin ◽  
Kristy Todd ◽  
A. Christine Argento ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Failure ◽  
Median Time ◽  
Prolonged Mechanical Ventilation ◽  
Percutaneous Tracheostomy ◽  
Tertiary Care ◽  
Severe Respiratory Failure ◽  
Spearman Correlation ◽  
Early Tracheostomy ◽  
Lengths Of Stay

ABSTRACTBackgroundSARS-CoV-2 can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary-care, urban teaching hospital.MethodsWe reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths-of-stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered <14 days of ventilation. Medians with interquartile ranges (IQR) were calculated and compared with Wilcoxon rank sum, Spearman correlation, Kruskal-Wallis, and regression modeling.ResultsFrom March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 – 24) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 – 0.37). No providers developed symptoms or tested positive for SARS-CoV-2.ConclusionsTracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.

scholarly journals AB083. Social media with cartoon characters as a powerful tool for expanding medical education and raising awareness of rare genetic diseases

2017 ◽  
Vol 5 (S2) ◽  
pp. AB083-AB083
Author(s):  
Thipwimol Tim-Aroon ◽  
Suphatcharee Leklab ◽  
Marin Satawiriya ◽  
Sirima Ketsuwan ◽  
Duangrurdee Wattanasirichaigoon
Keyword(s):  
Social Media ◽  
Medical Education ◽  
Genetic Diseases ◽  
Raising Awareness ◽  
Rare Genetic Diseases ◽  
Cartoon Characters

scholarly journals Case Report: First Two Identified Cases of Fabry Disease in Central Asia

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Cainelli ◽  
Dias Argandykov ◽  
Dauren Kaldarbekov ◽  
Murat Mukarov ◽  
Liên Tran Thi Phuong ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Central Asia ◽  
Genetic Diseases ◽  
Delayed Diagnosis ◽  
Specific Treatment ◽  
Organ Damage ◽  
Multisystem Disorder ◽  
Family Pedigree ◽  
Rare Genetic Diseases ◽  
Delays In Diagnosis

Background: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked inherited, genetic disease due to the functional deficiency of lysosomal α-galactosidase (α-GAL) that leads to the accumulation of glycosphingolipids (mainly globotriaosylceramide or Gb3) and its derivative globotriaosylsphingosine or lyso-Gb3. Classic FD is a multisystem disorder which initially presents in childhood with neuropathic pain and dermatological, gastrointestinal, ocular, and cochleo-vestibular manifestations. Over time, end-organ damage such as renal failure, cardiac arrhythmia and early stroke may develop leading to reduced life expectancy in the absence of specific treatment.Case presentation: We describe two Kazakh patients who presented in adulthood with a delayed diagnosis. We conducted also a family screening through cascade genotyping.Conclusion: This is the first description of cases of Fabry disease in Central Asia. An extensive family pedigree enabled the identification of ten additional family members. Patients with rare genetic diseases often experience substantial delays in diagnosis due to their rarity and non-specific symptoms, which can negatively impact their management and delay treatment. FD may be difficult to diagnose because of the non-specificity of its early and later-onset symptoms and its X-linked inheritance. Raising awareness of clinicians is important for earlier diagnosis and optimal outcome of specific therapies.

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