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Wien Med Wochenschr ; 171(5-6): 94-101, 2021 Apr.
Article En | MEDLINE | ID: mdl-33689085

Skeletal disorders are inherited disorders with significant skeletal involvement and most of them are rare or extremely rare. Based on the clinical, radiological and genetic phenotype, the group of skeletal disorder comprises more than 450 different and highly heterogeneous disorders. In skeletal disorders rapid and precise diagnoses are urgently needed for patient care and are based on the combination of clinical, radiological and genetic analysis. Novel genetic techniques have revolutionized diagnostics and have a huge impact on counseling of patients and families. Disease-specific long-term management in a multidisciplinary healthcare team in highly specialized centers is recommended to optimize care for these patients. Here we describe a multidisciplinary postnatal approach for the diagnosis and management of patients and families with rare skeletal disorders at the Vienna Bone and Growth Center. We discuss the value of a multidisciplinary diagnostic and management approach in the postnatal setting and provide a diagnostic flowchart for rare skeletal disorders.

Genetic Testing , Rare Diseases , Humans , Phenotype , Rare Diseases/diagnosis , Rare Diseases/therapy
BMJ Case Rep ; 14(2)2021 Feb 10.
Article En | MEDLINE | ID: mdl-33568404

We present a case of a 19-year-old man with right shoulder pain lasting for several months. Abdominal imaging revealed a right adrenal mass directly invading vascular structures into the right atrium. Widespread metastatic adrenocortical carcinoma was confirmed on biopsy. He opted for palliative mitotane treatment with home hospice care. This case emphasises the importance of considering abdominal masses in the differential diagnosis of persistent right shoulder pain after common causes have been ruled out. Early diagnosis could be potentially life-saving.

Adrenal Cortex Neoplasms/diagnosis , Adrenal Cortex Neoplasms/drug therapy , Adrenocortical Carcinoma/diagnosis , Adrenocortical Carcinoma/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Mitotane/therapeutic use , Shoulder Pain/diagnosis , Shoulder Pain/drug therapy , Adult , Fatal Outcome , Humans , Male , Rare Diseases/diagnosis , Rare Diseases/drug therapy , Young Adult
BMJ Case Rep ; 14(2)2021 Feb 10.
Article En | MEDLINE | ID: mdl-33568413

Cocaine, an alkaloid, is an addictive drug and its abuse as a recreational drug is on the increasing side with its associated complications. Gastrointestinal complications, after cocaine abuse, are less known and need to be addressed since the abuse is on the rise and the existing evidence is scarce. We report a case of a 22-year-old male patient who presented with abdominal pain following a cocaine injection. On examination, signs of peritonitis were noted and laparotomy revealed a 2×1 cm perforation in the distal ileum. The unhealthy intestinal segment was resected and taken out as a double-barrel ileostomy. The patient had an episode of severe lower gastrointestinal bleeding on postoperative day 6. CT and colonoscopy revealed signs of ischaemic bowel and tissue biopsy showed oedematous, inflamed and haemorrhagic bowel mucosa. The patient was managed conservatively and is doing well under follow-up in a de-addiction centre.

Cocaine-Related Disorders/complications , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/surgery , Intestinal Perforation/chemically induced , Intestinal Perforation/surgery , Rare Diseases/diagnosis , Rare Diseases/surgery , Adult , Humans , Male , Treatment Outcome , Young Adult
BMJ Case Rep ; 14(2)2021 Feb 12.
Article En | MEDLINE | ID: mdl-33579798

This is a rare case report of two filamentous fungi in a patient with contact lens related keratitis. An early corneal scrape may be useful in detecting multiple causative pathogens and aiding management. The main learning point is to consider fungal infections in patients with atypical ulcer appearances, as prompt diagnosis may reduce the morbidity burden.

Contact Lenses/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Fungi/isolation & purification , Keratitis/drug therapy , Keratitis/microbiology , Rare Diseases/drug therapy , Antifungal Agents/therapeutic use , Eye Infections, Fungal/diagnosis , Female , Fusarium/isolation & purification , Humans , Hypocreales/isolation & purification , Keratitis/diagnosis , Middle Aged , Rare Diseases/diagnosis , Rare Diseases/microbiology , Treatment Outcome , United Kingdom , Voriconazole/therapeutic use
Ann R Coll Surg Engl ; 103(2): e50-e52, 2021 Feb.
Article En | MEDLINE | ID: mdl-33559554

Appendix-associated hernias are extremely rare. They have been described sporadically in the literature, mostly as inguinal hernias. Appendix-associated incisional hernias are even more unusual. High clinical awareness is needed as complications can arise if misdiagnosis or delay occurs. We present an 80-year-old man with acute appendicitis in an incisional hernia. After successful surgery, the patient made a full recovery.

Appendectomy , Appendicitis/diagnosis , Herniorrhaphy/adverse effects , Incisional Hernia/diagnosis , Rare Diseases/diagnosis , Abdominal Pain/etiology , Abdominal Wall/surgery , Aged, 80 and over , Appendicitis/etiology , Appendicitis/surgery , Appendix/diagnostic imaging , Appendix/surgery , Hernia, Inguinal/surgery , Humans , Incisional Hernia/etiology , Incisional Hernia/surgery , Male , Nausea/etiology , Rare Diseases/etiology , Rare Diseases/surgery , Tomography, X-Ray Computed , Treatment Outcome , Vomiting/etiology
JAMA Netw Open ; 4(2): e2036220, 2021 02 01.
Article En | MEDLINE | ID: mdl-33630084

Importance: The Undiagnosed Diseases Network (UDN) is a national network that evaluates individual patients whose signs and symptoms have been refractory to diagnosis. Providing reliable estimates of admission outcomes may assist clinical evaluators to distinguish, prioritize, and accelerate admission to the UDN for patients with undiagnosed diseases. Objective: To develop computational models that effectively predict admission outcomes for applicants seeking UDN evaluation and to rank the applications based on the likelihood of patient admission to the UDN. Design, Setting, and Participants: This prognostic study included all applications submitted to the UDN from July 2014 to June 2019, with 1209 applications accepted and 1212 applications not accepted. The main inclusion criterion was an undiagnosed condition despite thorough evaluation by a health care professional; the main exclusion criteria were a diagnosis that explained the objective findings or a review of the records that suggested a diagnosis. A classifier was trained using information extracted from application forms, referral letters from health care professionals, and semantic similarity between referral letters and textual description of known mendelian disorders. The admission labels were provided by the case review committee of the UDN. In addition to retrospective analysis, the classifier was prospectively tested on another 288 applications that were not evaluated at the time of classifier development. Main Outcomes and Measures: The primary outcomes were whether a patient was accepted or not accepted to the UDN and application order ranked based on likelihood of admission. The performance of the classifier was assessed by comparing its predictions against the UDN admission outcomes and by measuring improvement in the mean processing time for accepted applications. Results: The best classifier obtained sensitivity of 0.843, specificity of 0.738, and area under the receiver operating characteristic curve of 0.844 for predicting admission outcomes among 1212 accepted and 1210 not accepted applications. In addition, the classifier can decrease the current mean (SD) UDN processing time for accepted applications from 3.29 (3.17) months to 1.05 (3.82) months (68% improvement) by ordering applications based on their likelihood of acceptance. Conclusions and Relevance: A classification system was developed that may assist clinical evaluators to distinguish, prioritize, and accelerate admission to the UDN for patients with undiagnosed diseases. Accelerating the admission process may improve the diagnostic journeys for these patients and serve as a model for partial automation of triaging or referral for other resource-constrained applications. Such classification models make explicit some of the considerations that currently inform the use of whole-genome sequencing for undiagnosed disease and thereby invite a broader discussion in the clinical genetics community.

Machine Learning , Patient Selection , Rare Diseases/diagnosis , Referral and Consultation , Undiagnosed Diseases/diagnosis , Adolescent , Adult , Area Under Curve , Child , Child, Preschool , Computer Simulation , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Patient Admission , Prospective Studies , ROC Curve , Rare Diseases/genetics , Reproducibility of Results , Retrospective Studies , Triage , Undiagnosed Diseases/genetics , Whole Genome Sequencing , Young Adult
BMJ Case Rep ; 14(1)2021 Jan 11.
Article En | MEDLINE | ID: mdl-33431446

Primary Bartholin gland carcinoma (BGC) is an extremely rare disease. It typically presents in elderly women. It can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment. We are presenting a case report of BGC in a 35-year-old woman, which has created a diagnostic as well as therapeutic dilemma.

Bartholin's Glands/pathology , Carcinoma/diagnosis , Cysts/diagnosis , Rare Diseases/diagnosis , Vulvar Neoplasms/diagnosis , Adult , Age of Onset , Bartholin's Glands/diagnostic imaging , Bartholin's Glands/surgery , Carcinoma/pathology , Carcinoma/surgery , Cysts/pathology , Cysts/surgery , Female , Humans , Magnetic Resonance Imaging , Premenopause , Rare Diseases/pathology , Rare Diseases/surgery , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery
Int J Mol Sci ; 22(2)2021 Jan 12.
Article En | MEDLINE | ID: mdl-33445477

There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].

Biomarkers , Rare Diseases/diagnosis , Rare Diseases/etiology , Rare Diseases/therapy , Disease Management , Disease Susceptibility , Humans
Article Ru | MEDLINE | ID: mdl-33161658

The study was carried out to analyze detection of rare diseases that are not included into listings of rare (orphan) diseases to be treated at the expense of budget resources of the Russian Federation Russian Federation (hereinafter referred as rare diseases out of reimbursement). The analysis of detection of patients with rare diseases out of reimbursement in Russian Federation was carried out. The information was collected and summarized on the basis of open sources by the way of formalized personal request to the heads of patient and public organizations providing care of patients with rare diseases out of reimbursement. It is established that in the Russian Federation (85 subjects) reside patients with more than 250 forms and groups of rare diseases and only 28 out of them are included into the Federal registries of patients. Actually, there are more than 8 000 nosologic forms of rare diseases that are known thus far. The monitoring permitted to collect data concerning 30 particular nosological forms and groups of rare diseases out of reimbursement. Among them, 23 out of 30 analyzed pathologies have genetic nature. And only for 24 out of 30 diseases the registration of patients is applied. It is necessary to organize modern system of registration of patients within the framework of the Federal registry that includes full and actual data about patients, course of disease, therapeutic interventions that will permit to determine prevalence, disability, mortality, lethality, necessary medicinal maintenance and also to establish spectrum of diseases that are to be included into drug reimbursement programs.

Orphan Drug Production , Rare Diseases , Humans , Prevalence , Rare Diseases/diagnosis , Rare Diseases/drug therapy , Rare Diseases/epidemiology , Registries , Russia/epidemiology
Article En | MEDLINE | ID: mdl-32824597

Background: Increasing attention is being paid to improve the quality of life of patients with rare diseases in China. However, we are currently unaware of the problems encountered in the medical services of rare diseases from the viewpoints of doctors and patients. This study addressed the differences in the perceived barriers of diagnosis and treatments for rare diseases between doctors and patients in China. Methods: Two independent cross-sectional surveys on the perception of Chinese doctors' and patients' experiences with rare diseases were launched online between January and February 2018. A non-probability, convenience sampling method was employed to recruit participants. Results: In all, 45 rare diseases were reported by 139 doctors and 1853 patients. Patients with rare diseases faced significantly more difficulties in receiving accurate diagnosis (72.0%) and accessing information related to diagnosis and treatment (77.3%) as compared with doctors (34.5% and 40.3%, p < 0.0001, respectively). Specially, patients felt more difficulties than doctors in obtaining sustainable treatment for rare diseases (84.3% vs. 49.6%, p < 0.001). A higher percentage of patients (58.7%) than that of doctors (39.1%) had concerns in terms of the affordability of drugs. Further, 66.3% patients claimed that the drugs used to treat their conditions were not covered by their current medical insurances, whereas only 21.6% for doctors (p < 0.0001). Moreover, 35.3% of doctors responded that they recommended patients to visit the specialist they knew or were acquainted with, whereas 30.0% of patients said that their doctors chose to treat them based on their past experiences (p < 0.001). Conclusion: The perceived experience of patients with regard to diagnosis and treatment was significantly different from that of doctors. An integrated medical service platform should be established to facilitate better communication and mutual understanding of rare diseases between patients and doctors.

Quality of Life , Rare Diseases , Adolescent , Adult , Aged , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Rare Diseases/diagnosis , Rare Diseases/therapy , Surveys and Questionnaires , Young Adult
Am J Hum Genet ; 107(3): 403-417, 2020 09 03.
Article En | MEDLINE | ID: mdl-32755546

Human Phenotype Ontology (HPO)-based analysis has become standard for genomic diagnostics of rare diseases. Current algorithms use a variety of semantic and statistical approaches to prioritize the typically long lists of genes with candidate pathogenic variants. These algorithms do not provide robust estimates of the strength of the predictions beyond the placement in a ranked list, nor do they provide measures of how much any individual phenotypic observation has contributed to the prioritization result. However, given that the overall success rate of genomic diagnostics is only around 25%-50% or less in many cohorts, a good ranking cannot be taken to imply that the gene or disease at rank one is necessarily a good candidate. Here, we present an approach to genomic diagnostics that exploits the likelihood ratio (LR) framework to provide an estimate of (1) the posttest probability of candidate diagnoses, (2) the LR for each observed HPO phenotype, and (3) the predicted pathogenicity of observed genotypes. LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) placed the correct diagnosis within the first three ranks in 92.9% of 384 case reports comprising 262 Mendelian diseases, and the correct diagnosis had a mean posttest probability of 67.3%. Simulations show that LIRICAL is robust to many typically encountered forms of genomic and phenomic noise. In summary, LIRICAL provides accurate, clinically interpretable results for phenotype-driven genomic diagnostics.

Computational Biology , Databases, Genetic , Genomics , Rare Diseases/diagnosis , Algorithms , Exome/genetics , Humans , Phenotype , Rare Diseases/genetics , Software
Fortschr Neurol Psychiatr ; 88(8): 528-531, 2020 Aug.
Article De | MEDLINE | ID: mdl-32634845

Posterior cortical atrophy (PCA) is a rare neurodegenerative disease, which manifests with complex visual disturbances. PCA can present in isolation ('PCA-pure') or in association with other neurodegenerative disorders ('PCA-plus'). Diagnosis is nevertheless frequently delayed, as PCA is a less known disease entity and initially a primary ocular disease is taken into consideration.

Atrophy/pathology , Cerebral Cortex/pathology , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/pathology , Vision Disorders/diagnosis , Delayed Diagnosis , Humans , Rare Diseases/diagnosis , Rare Diseases/pathology , Syndrome , Vision Disorders/pathology
Folia Med Cracov ; 60(1): 55-60, 2020.
Article En | MEDLINE | ID: mdl-32658212

An incarcerated epigastric hernia (localized in linea alba) is a very rare observation. Here, we present a case of a 66-year-old white male who was admitted to the emergency department due to vomiting and epigastric pain. On physical examination, the only observed abnormality was a painless soft epigastric tumor located in the upper midline, measuring about 12 cm in diameter. The patient claimed that he had the tumor for more than 30 years and it never changed in diameter nor caused him any discomfort. A lipoma was initially suspected. However, an ultrasound of the abdomen revealed an incarcerated stomach, trapped due to the defect in the epigastric abdominal wall. The patient was sent for surgery and the presence of an incarcerated epigastric hernia of the linea alba, which contained the anterior wall of the stomach was confirmed. The presented case confirms that the use of ultrasonography may be an effective method to recognize unusual types of hernias, and that ultrasonography should be routinely used in emergency departments.

Epigastric Arteries/surgery , Hernia, Abdominal/diagnosis , Hernia, Abdominal/surgery , Herniorrhaphy/methods , Rare Diseases/diagnosis , Rare Diseases/surgery , Ultrasonography/methods , Aged , Humans , Male , Preoperative Period , Treatment Outcome
Nature ; 583(7814): 96-102, 2020 07.
Article En | MEDLINE | ID: mdl-32581362

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

Internationality , National Health Programs , Rare Diseases/diagnosis , Rare Diseases/genetics , Whole Genome Sequencing , Actin-Related Protein 2-3 Complex/genetics , Adaptor Proteins, Signal Transducing/genetics , Alleles , Databases, Factual , Erythrocytes/metabolism , GATA1 Transcription Factor/genetics , Humans , Phenotype , Quantitative Trait Loci , Receptors, Thrombopoietin/genetics , State Medicine , United Kingdom
HNO ; 68(8): 581-589, 2020 Aug.
Article De | MEDLINE | ID: mdl-32583063

BACKGROUND: Silent sinus syndrome (SSS), organized hematoma (OH), and pneumosinus dilatans (PD) are rare, usually unilateral diseases of the maxillary sinus. Due to misinterpretation, excessive diagnostics and unnecessarily aggressive surgery or a delay in diagnostics and treatment are common. OBJECTIVE: The objective of this study was to develop reasonable and comprehensible diagnostic criteria to improve diagnosis and treatment of these rare diseases. METHODS: In this retrospective study, all patients treated for SSS, OH, and PD from 2012 to 2019 were identified. Patient history, diagnostic tests and results, and postoperative course were analyzed and compared with the available literature. RESULTS: During the study period, 7 patients with SSS, 3 patients with PD, and 2 patients with OH were treated and available for follow-up. Comparison of these patients with the literature allowed us to develop diagnostic criteria. CONCLUSION: Medical history combined with endoscopic and radiologic criteria should improve preoperative diagnosis of these three rare diseases of the maxillary sinus and help to distinguish them from other differential diagnoses. This approach should minimize morbidity for the patients.

Maxillary Sinus , Paranasal Sinus Diseases , Rare Diseases , Humans , Paranasal Sinus Diseases/diagnosis , Rare Diseases/diagnosis , Retrospective Studies , Tomography, X-Ray Computed
BMC Infect Dis ; 20(1): 366, 2020 May 24.
Article En | MEDLINE | ID: mdl-32448208

BACKGROUND: Kosakonia cowanii, formerly known as Enterobacter cowanii, is a Gram-negative bacillus belonging to the order Enterobacterales. The species is usually recognized as a plant pathogen and has only anecdotally been encountered as a human pathogen. Here we describe the rare case of a K. cowanii infection presenting as an acute cholecystitis and provide a review of available literature. Evident difficulties in species identification by biochemical profiling suggests that potentially, K. cowanii might represent an underestimated human pathogen. CASE PRESENTATION: A 61-year old immunocompromised man presented to the hospital with fever and pain in the upper right abdomen. Sonography revealed an inflamed gall bladder and several gall stones. A cholecystectomy proved diagnosis of an acute cholecystitis with a partial necrosis of the gall bladder. Surgical specimen grew pure cultures of Gram-negative rods unambiguously identified as K. cowanii by MALDI-TOF, 16S-rRNA analysis and whole genome sequencing. CONCLUSIONS: Reporting cases of Kosakonia species can shed light on the prevalence and clinical importance of this rare cause of human infection. Our case is the first to describe an infection without prior traumatic inoculation of the pathogen from its usual habitat, a plant, to the patient. This raises the question of the route of infections as well as the pathogen's ability to colonize the human gut.

Cholecystitis, Acute/diagnosis , Cholecystitis, Acute/microbiology , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae/genetics , Rare Diseases/diagnosis , Rare Diseases/microbiology , Cholecystectomy , Enterobacteriaceae Infections/microbiology , Gallbladder/pathology , Gallstones/surgery , Humans , Immunocompromised Host , Male , Middle Aged , Necrosis , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Treatment Outcome , Whole Genome Sequencing
Ned Tijdschr Geneeskd ; 1642020 04 30.
Article Nl | MEDLINE | ID: mdl-32395952

According to the European definition, rare diseases are life-threatening or chronically debilitating conditions that affect only 5 out of 10,000 people in the European Union. It is estimated that there are around 6000-8000 different rare diseases, affecting 6-8% of the population in the course of their lives. For the Netherlands, this means that about 1 million people are affected by a rare disease, or one in 17 people. Patients with rare diseases indicate that they often have a long and uncertain diagnostic journey behind them, while the first symptoms present in childhood in 75% of the rare diseases. In this perspective, we discuss some of the results from the research report 'Scherperzicht op diagnostischevertragingbijzeldzameaandoeningen' in which the diagnostic journey for patients with rare diseases is mapped out with figures. We also make recommendations to speed up the diagnostic process for patients with rare diseases.

Delayed Diagnosis/trends , Rare Diseases/diagnosis , Adult , Child , European Union , Female , Humans , Male , Netherlands/epidemiology , Rare Diseases/epidemiology
Ned Tijdschr Geneeskd ; 1642020 04 30.
Article Nl | MEDLINE | ID: mdl-32395955

Not only rare diseases are uncommon. There are also rare presentations of common diseases, not to mention rare side effects of infrequently prescribed or new drugs. Not all of these rare disease presentations have a genetic causal component. Additional (genetic or non-genetic) ancillary diagnostic tests, in which some of the inevitably occurring chance findings will present us with new problems, are not the solution for this problem, nor are disease or therapy oriented centres of expertise. The solution should be sought in pattern recognition; not by the individual physician, but through collaboration of physicians who take the time to give meaning to carefully obtained clinical parameters in individual patients. The size and composition of such a - often ad hoc - partnership should be adapted to each individual situation.

Interdisciplinary Communication , Patient Care Management/methods , Rare Diseases/diagnosis , Diagnosis, Differential , Humans