Int J Mol Sci. 2023 May 22;24(10):9064. doi: 10.3390/ijms24109064.

ABSTRACT

Rare Diseases (RD) do not have an exact definition since local authorities define the criteria in different ways, from fewer than 5 people in 10,000, according to the European Union, to the standard world average of 40 cases per 100,000 people [...].

PMID:37240412 | PMC:PMC10219232 | DOI:10.3390/ijms24109064

Orphanet J Rare Dis. 2023 May 24;18(1):123. doi: 10.1186/s13023-023-02728-z.

ABSTRACT

BACKGROUND: Osteogenesis imperfecta (OI) is a group of rare inheritable disorders of connective tissue. The cardinal manifestations of OI are low bone mass and reduced bone mineral strength, leading to increased bone fragility and deformity that may lead to significant impairment in daily life. The phenotypic manifestations show a broad range of severity, ranging from mild or moderate to severe and lethal. The here presented meta-analysis aimed to analyze existing findings on quality of life (QoL) in children and adults with OI.

METHODS: Nine databases were searched with predefined key words. The selection process was executed by two independent reviewers and was based on predetermined exclusion and inclusion criteria. The quality of each study was assessed using a risk of bias tool. Effect sizes were calculated as standardized mean differences. Between-study heterogeneity was calculated with the I2 statistic.

RESULTS: Among the studies included two featured children and adolescents (N = 189), and four adults (N = 760). Children with OI had significantly lower QoL on the Pediatric quality of life inventory (PedsQL) with regards to the total score, emotional, school, and social functioning compared to controls and norms. The data was not sufficient to calculate differences regarding OI-subtypes. In the adult sample assessed with Short Form Health Survey Questionnaire, 12 (SF-12) and 36 items (SF-36), all OI types showed significantly lower QoL levels across all physical component subscales compared to norms. The same pattern was found for the mental component subscales namely vitality, social functioning, and emotional role functioning. The mental health subscale was significantly lower for OI type I, but not for type III and IV. All of the included studies exhibited a low risk of bias.

CONCLUSIONS: QoL was significantly lower in children and adults with OI compared to norms and controls. Studies in adults comparing OI subtypes showed that the clinical severity of the phenotype is not related to worse mental health QoL. Future research is needed to examine QoL in children and adolescents in more sophisticated ways and to better understand the association between clinical severity of an OI-phenotype/severity and mental health in adults.

PMID:37226194 | DOI:10.1186/s13023-023-02728-z

Orphanet J Rare Dis. 2023 May 24;18(1):122. doi: 10.1186/s13023-023-02731-4.

ABSTRACT

BACKGROUND: Wilson disease (WD) is a rare, hereditary disorder of copper metabolism. Due to its variable symptoms and manifestations, diagnosis remains challenging. Affected patients must obtain lifelong medical treatment, as the disease is fatal if untreated. Patients require continuous monitoring, but little is known about the care of these patients in Germany. Therefore, we analyzed the medical care of WD patients at German university centers. We sent a questionnaire containing 20 questions to a total of 108 departments of pediatrics, neurology and gastroenterology in 36 university hospitals. Our questions referred to the characteristics of WD patients at the different sites and internal procedures regarding diagnosis, therapy and follow-up. A descriptive statistical analysis was performed.

RESULTS: Sixty-three departments (58%) returned our questionnaire. In total, approximately one-third of the estimated WD patients in Germany are seen annually in the outpatient clinics of these departments (approx. 950 patients). There are only a few departments which treat patients in a multidisciplinary setting (12%). Our survey revealed that for diagnosis, 51% of all departments used an algorithm based on the Leipzig score as recommended by international guidelines. Most departments apply essential parameters recommended by WD guidelines. Routine monitoring is performed at least biannually by 84% of the departments, and standard investigations for monitoring are regularly applied. A routine family screening is performed by 84% of all departments. A reduction in medical therapy during pregnancy is recommended by 46% of the departments. Only 14% suggested that WD patients should not breastfeed. Liver transplantation (LT) due to WD is a rare but repeatedly occurring event. Most departments of gastroenterology (72%) reported at least one patient with LT within the last decade.

CONCLUSIONS: Medical care of WD patients at German university centers follows the recommendations set forth by international guidelines, but only a few centers treat significant numbers of patients. The surveillance of patients does not follow specified standards, but most departments adhere to the accepted guidelines. The formation of central units and networks in a multidisciplinary setting should be evaluated to improve the care of WD patients.

PMID:37226184 | DOI:10.1186/s13023-023-02731-4

BMC Pediatr. 2023 May 24;23(1):259. doi: 10.1186/s12887-023-04077-z.

ABSTRACT

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a rare genetic disorder characterized with the development of multiple benign tumors on the nerves and skin.

CASE PRESENTATION: This report described a neonatal case with a large mass observed on the left side of the maxillofacial and cervical region at birth. Meantime, multiple cafe-au-lait macules (CALMs) were seen on the trunk and both lower extremities.

CONCLUSIONS: In this case, the clinical features of the rare NF1 neonate are discussed along with its ultrasound findings.

PMID:37226143 | DOI:10.1186/s12887-023-04077-z

Rev Gastroenterol Peru. 2023 Jan-Mar;43(1):65-68.

ABSTRACT

Colonic malacoplakia is an unusual cause of chronic diarrhea, and it may present as a consumptive disease. At the colon, it can induce ulcerative and erosive nodular lesions, that mimic other common granulomatous or infectious diseases. Diagnosis is support in biopsies showing groups of histiocytes, with typical Michaelis-Gutmann inclusions, which are positive with the Von Kossa stain. We present the case of a 55-year-old male, without associated diseases, who presented with diarrhea, weight loss and anemia, showing a very good clinical response to antibiotics.

PMID:37226073

BMC Cardiovasc Disord. 2023 May 23;23(1):267. doi: 10.1186/s12872-023-03289-6.

ABSTRACT

BACKGROUND: Kounis syndrome is a rare clinical condition characterized by the occurrence of an acute coronary event induced by an acute allergic episode. The ongoing pandemic of coronavirus disease 2019 (COVID-19) has contributed to an increase in the incidence of allergic reactions to a certain extent, thereby increasing the incidence of Kounis syndrome. Timely diagnosis and effective management of this disease are important in clinical practice.

CASE PRESENTATION: We report a 43-year-old woman who developed generalized pruritus, breathlessness, paroxysmal precordial crushing pain, and dyspnea after receiving the third dose of the COVID-19 vaccine. After anti-allergic treatment and therapy for acute myocardial ischemia, her symptoms resolved with improvement in cardiac function and resolution of ST-segment changes. The prognosis was satisfactory, and the final diagnosis was type I Kounis syndrome.

CONCLUSION: This patient with type I Kounis syndrome rapidly developed acute coronary syndrome (ACS) after an acute allergic reaction to the COVID-19 vaccine. ​Timely diagnosis of acute allergic reaction and ACS, and targeted treatment based on the relevant guidelines are the key to successful treatment of the syndrome.​.

PMID:37221464 | DOI:10.1186/s12872-023-03289-6

BMJ Case Rep. 2023 May 23;16(5):e254113. doi: 10.1136/bcr-2022-254113.

ABSTRACT

Infectious scleritis is a rare disease entity with potentially devastating visual sequelae. Here we present the clinical history, work-up and aetiology of an unusual case of infectious scleritis.

PMID:37221000 | DOI:10.1136/bcr-2022-254113

Dermatol Online J. 2023 Apr 15;29(2). doi: 10.5070/D329260772.

ABSTRACT

A 75-year-old man with a three-year history of metastatic lung adenocarcinoma was diagnosed with cutaneous lymphangitic carcinomatosa of unique morphology. He was admitted to our hospital for right neck swelling, erythema, and failure to thrive. Skin examination demonstrated an indurated, thickened, firm, hyperpigmented plaque extending from the right neck and chest to the right ear, cheek, and eyelids. Skin biopsy demonstrated poorly differentiated adenocarcinoma, morphologically consistent with metastasis from the patient's known pulmonary adenocarcinoma and showed dermal invasion, perineural invasion, and involvement of dermal lymphatics. The diagnosis was an atypical presentation of cutaneous lymphangitis carcinomatosa from metastatic lung adenocarcinoma. This case presentation affirms that cutaneous lymphangitis carcinomatosa has a variety of atypical presentations, so physicians must maintain a high index of suspicion when evaluating cutaneous lesions in patients with known or suspected internal malignancy.

PMID:37220288 | DOI:10.5070/D329260772

BMC Med Res Methodol. 2023 May 20;23(1):121. doi: 10.1186/s12874-023-01947-z.

ABSTRACT

BACKGROUND: There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.

METHODS: Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable.

RESULTS: Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier's gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet's syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington's disease, Sjogren's syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.

CONCLUSIONS: Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.

PMID:37210484 | DOI:10.1186/s12874-023-01947-z

JNMA J Nepal Med Assoc. 2023 Apr 1;61(260):379-382. doi: 10.31729/jnma.8116.

ABSTRACT

Toxic epidermal necrolysis in pregnancy is a rare disease that can have an adverse effect on Toxic epidermal necrolysis in pregnancy is a rare disease that can have an adverse effect on pregnancy outcomes. Common etiology of the condition includes medication triggered followed by mycoplasma infection. Almost one-third of cases are idiopathic. Despite the rarity of data, terbinafine causing toxic epidermal necrolysis has been reported. Toxic epidermal necrolysis manifests as a macule, erythema followed by a blister in the chest and spreading to other parts of the body. Removal of the offending agent and supportive management is the cornerstone of management. Here we report 22-year-old primipara pregnant women presenting with toxic epidermal necrolysis after 3 weeks of oral terbinafine use with good pregnancy outcomes.

KEYWORDS: case reports; pregnancy; Stevens-Johnson syndrome; toxic epidermal necrolysis.

PMID:37208883 | PMC:PMC10089020 | DOI:10.31729/jnma.8116

Hum Genomics. 2023 May 19;17(1):44. doi: 10.1186/s40246-023-00491-7.

ABSTRACT

BACKGROUND: Ubiquitin-related rare diseases are generally characterized by developmental delays and mental retardation, but the exact incidence or prevalence is not yet fully understood. The clinical application of next-generation sequencing for pediatric seizures and developmental delay of unknown causes has become common in studies aimed at identification of a causal gene in patients with ubiquitin-related rare diseases that cannot be diagnosed using conventional fluorescence in situ hybridization or chromosome microarray tests. Our study aimed to investigate the effects of ubiquitin-proteasome system on ultra-rare neurodevelopmental diseases, through functional identification of candidate genes and variants.

METHODS: In our present work, we carried out genome analysis of a patient with clinical phenotypes of developmental delay and intractable convulsion, to identify causal mutations. Further characterization of the candidate gene was performed using zebrafish, through gene knockdown approaches. Transcriptomic analysis using whole embryos of zebrafish knockdown morphants and additional functional studies identified downstream pathways of the candidate gene affecting neurogenesis.

RESULTS: Through trio-based whole-genome sequencing analysis, we identified a de novo missense variant of the ubiquitin system-related gene UBE2H (c.449C>T; p.Thr150Met) in the proband. Using zebrafish, we found that Ube2h is required for normal brain development. Differential gene expression analysis revealed activation of the ATM-p53 signaling pathway in the absence of Ube2h. Moreover, depletion of ube2h led to induction of apoptosis, specifically in the differentiated neural cells. Finally, we found that a missense mutation in zebrafish, ube2h (c.449C>T; p.Thr150Met), which mimics a variant identified in a patient with neurodevelopmental defects, causes aberrant Ube2h function in zebrafish embryos.

CONCLUSION: A de novo heterozygous variant in the UBE2H c.449C>T (p.Thr150Met) has been identified in a pediatric patient with global developmental delay and UBE2H is essential for normal neurogenesis in the brain.

PMID:37208785 | PMC:PMC10199504 | DOI:10.1186/s40246-023-00491-7

BMC Public Health. 2023 May 19;23(1):910. doi: 10.1186/s12889-023-15654-3.

ABSTRACT

BACKGROUND: Work participation is a crucial aspect of health outcome and an important part of life for most people with rare genetic diseases. Despite that work participation is a social determinant of health and seems necessary for understanding health behaviours and quality of life, it is an under-researched and under-recognized aspect in many rare diseases. The objectives of this study was to map and describe existing research on work participation, identify research gaps, and point to research agendas in a selection of rare genetic diseases.

METHODS: A scoping review was performed by searching relevant literature in bibliographic databases and other sources. Studies addressing work participation in people with rare genetic diseases published in peer reviewed journals were assessed using EndNote and Rayyan. Data were mapped and extracted based on the research questions concerning the characteristics of the research.

RESULTS: Of 19,867 search results, 571 articles were read in full text, and 141 satisfied the eligibility criteria covering 33 different rare genetic diseases; 7 were reviews and 134 primary research articles. In 21% of the articles the primary aim was to investigate work participation. The extent of studies varied between the different diseases. Two diseases had more than 20 articles, but most had only one or two articles. Cross-sectional quantitative studies were predominant, with few utilizing prospective or qualitative design. Nearly all articles (96%) reported information about work participation rate, and 45% also included information about factors associated with work participation and work disability. Due to differences in methodologies, cultures and respondents, comparison between and within diseases are difficult. Nevertheless, studies indicated that many people with different rare genetic diseases experience challenges related to work, closely associated to the symptoms of the disease.

CONCLUSION: While studies indicate high prevalence of work disability in many patients with rare diseases, the research is scarce and fragmented. More research is warranted. Information about the unique challenges of living with different rare diseases is crucial for health and welfare systems to better facilitate work participation. In addition, the changing nature of work in the digital age, may also open up new possibilities for people with rare genetic diseases and should be explored.

PMID:37208707 | PMC:PMC10197424 | DOI:10.1186/s12889-023-15654-3

Stud Health Technol Inform. 2023 May 18;302:607-608. doi: 10.3233/SHTI230216.

ABSTRACT

The common occurrence of characteristic symptoms can be used to infer diagnoses. The aim of this study is to show how syndrome similarity analysis using given phenotypic profiles can help in the diagnosis of rare diseases. HPO was used to map syndromes and phenotypic profiles. The system architecture described is planned to be implemented in a clinical decision support system for unclear diseases.

PMID:37203759 | DOI:10.3233/SHTI230216

Stud Health Technol Inform. 2023 May 18;302:358-359. doi: 10.3233/SHTI230139.

ABSTRACT

Rare diseases are commonly defined by an incidence of less than 5/10000 inhabitants. There are some 8000 different rare diseases known. So even if a single rare disease is seldom, together they pose a relevant problem for diagnosis and treatment. This is especially true if a patient is treated for another common disease. University hospital of Gießen is part of the CORD-MI Project on rare diseases within the German Medical Informatics Initiative (MII) and a member of the MIRACUM consortium within the MII. As part of the ongoing Development for a clinical research study monitor within the use case 1 of MIRACUM, the study monitor has been configured to detect patients with rare diseases during their routine clinical encounters. The goal was to send a documentation request to the corresponding patient chart within the patient data management system for extended disease documentation to enhance clinical awareness for the patients' potential problems. The project was started in late 2022 and has so far been successfully tuned to detect patients with Mucoviscidosis and place notifications within the patient chart of the patient data management system (PDMS) on intensive care units.

PMID:37203683 | DOI:10.3233/SHTI230139

Stud Health Technol Inform. 2023 May 18;302:292-296. doi: 10.3233/SHTI230121.

ABSTRACT

The project "Collaboration on Rare Diseases" CORD-MI connects various university hospitals in Germany to collect sufficient harmonized electronic health record (EHR) data for supporting clinical research in the field of rare diseases (RDs). However, the integration and transformation of heterogeneous data into an interoperable standard through Extract-Transform-Load (ETL) processes is a complex task that may influence the data quality (DQ). Local DQ assessments and control processes are needed to ensure and improve the quality of RD data. We therefore aim to investigate the impact of ETL processes on the quality of transformed RD data. Seven DQ indicators for three independent DQ dimensions were evaluated. The resulting reports show the correctness of calculated DQ metrics and detected DQ issues. Our study provides the first comparison results between the DQ of RD data before and after ETL processes. We found that ETL processes are challenging tasks that influence the quality of RD data. We have demonstrated that our methodology is useful and capable of evaluating the quality of real-world data stored in different formats and structures. Our methodology can therefore be used to improve the quality of RD documentation and to support clinical research.

PMID:37203665 | DOI:10.3233/SHTI230121

Stud Health Technol Inform. 2023 May 18;302:1037-1041. doi: 10.3233/SHTI230342.

ABSTRACT

In the context of medical concept extraction, it is critical to determine if clinical signs or symptoms mentioned in the text were present or absent, experienced by the patient or their relatives. Previous studies have focused on the NLP aspect but not on how to leverage this supplemental information for clinical applications. In this paper, we aim to use the patient similarity networks framework to aggregate different phenotyping modalities. NLP techniques were applied to extract phenotypes and predict their modalities from 5470 narrative reports of 148 patients with ciliopathies (a group of rare diseases). Patient similarities were computed using each modality separately for aggregation and clustering. We found that aggregating negated phenotypes improved patient similarity, but further aggregating relatives' phenotypes worsened the result. We suggest that different modalities of phenotypes can contribute to patient similarity, but they should be aggregated carefully and with appropriate similarity metrics and aggregation models.

PMID:37203576 | DOI:10.3233/SHTI230342

Int J Equity Health. 2023 May 17;22(1):93. doi: 10.1186/s12939-023-01903-9.

ABSTRACT

BACKGROUND: Rare diseases (RDs) are difficult to diagnose and expensive to treat. Thus, the South Korean government has implemented several policies to help RD patients, including the Medical Expense Support Project, supporting low- to middle-income RD patients. However, no study in Korea has yet addressed health inequity in RD patients. This study assessed inequity trends in the medical utilization and expenditures of RD patients.

METHODS: This study measured the horizontal inequity index (HI) of RD patients and an age- and sex-matched control group using the National Health Insurance Service data from 2006 to 2018. Sex, age, number of chronic diseases, and disability variables were used to model expected medical needs and adjust the concentration index (CI) for medical utilization and expenditures.

RESULTS: The HI index of healthcare utilization in RD patients and the control group ranged from -0.0129 to 0.0145, increasing until 2012 and fluctuating since then. This increasing trend was more apparent for inpatient utilization in the RD patient group than in the outpatient group. The same index in the control group ranged from -0.0112 to -0.0040 without a significant trend. The healthcare expenditure HI in RD patients rose from -0.0640 to -0.0038, showing pro-poor values but moving toward a pro-rich state. In the control group, the HI for healthcare expenditures remained between 0.0029 and 0.0085.

CONCLUSIONS: The HI of inpatient utilization and inpatient expenditures increased in a pro-rich state. The study results showed that implementing a policy that supports inpatient service utilization could help achieve health equity for RD patients.

PMID:37198638 | DOI:10.1186/s12939-023-01903-9

Nat Rev Drug Discov. 2023 Jun;22(6):440-441. doi: 10.1038/d41573-023-00082-0.

NO ABSTRACT

PMID:37193741 | DOI:10.1038/d41573-023-00082-0

Biomedicines. 2023 Apr 20;11(4):1226. doi: 10.3390/biomedicines11041226.

ABSTRACT

Asthma affects 10% of the worldwide population; about 5% of cases are severe with the need for target therapies such as biologics. All the biologics approved for asthma hit the T2 pathway of inflammation. T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and Type-17 inflammation and the neutrophilic form that accounts for 20-30% of all patients with asthma. Neutrophilic asthma's prevalence is even higher in patients with severe or refractory asthma. We searched Medline and PubMed archives from the past ten years for articles with the subsequent titles: "neutrophilic asthma", "non-type 2 asthma" and "paucigranulocytic asthma". We identified 177 articles; 49 were considered relevant by the title and 33 by the reading of the abstract. Most of these articles are reviews (n = 19); only 6 are clinical trials. No study identified an effective treatment. We used the literature reported by these articles to search for further biologic treatments that target pathways different from T2. We identified 177 articles, 93 of which were considered relevant for the review and included in the present article. In conclusion, T2-low asthma remains poorly investigated in terms of biomarkers, especially as a therapeutic orphan disease.

PMID:37189844 | DOI:10.3390/biomedicines11041226

Taiwan J Obstet Gynecol. 2023 May;62(3):440-443. doi: 10.1016/j.tjog.2022.12.011.

ABSTRACT

OBJECTIVE: Wolfram Syndrome (WS) is a rare autosomal recessive neurodegenerative disorder caused by mutations in WFS1 or CISD2 (WFS2). We present a rare case report of pregnancy with WFS1 spectrum disorder (WFS1-SD) in our hospital and reviewed literature to provide the management of pregnancy in these patients through multi-disciplinary cooperation.

CASE REPORT: A 31-year-old (gravida 6, para 1) woman with WFS1-SD conceived naturally. During the pregnancy, she adjusted insulin intermittently to control blood glucose and monitored intraocular pressure changes under the guidance of doctors without any complications. Cesarean section was delivered at 37+4 weeks of gestation due to breech position and uterine scar and the neonatal weight was 3200 g. Apgar score 10 at 1 min, 10 at 5-min and 10 at 10 min, respectively. This rare case had a good maternal and infant outcome under multidisciplinary management.

CONCLUSION: WS is an extremely rare disease. Limited information is available on the impact and management of WS on maternal physiologic adaptation and fetal outcome. This case provide a guide for clinicians to raise awareness of this rare disease and strengthen the management of pregnancy in these patients.

PMID:37188450 | DOI:10.1016/j.tjog.2022.12.011