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Orphanet Journal of Rare Diseases May 2023Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally... (Review)
Review
INTRODUCTION
Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke.
METHODS
A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.
RESULTS
The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0-720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.
CONCLUSION
Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.
Topics: Male; Female; Humans; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Phenotype; Stroke; Mutation
PubMed: 37179309
DOI: 10.1186/s13023-023-02721-6 -
Frontiers in Cellular and Infection... 2022() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of...
() is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with in recent years. The disseminated infection of can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in , , , , and . was detected in both the blood and lymph nodes of P1 with mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing infection were 100% and 98.7%, respectively. The reporting time for detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. infection was first reported in IEI patients with gene mutation, which expanded the IEI lineage susceptible to . For IEI patients with infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.
Topics: Antifungal Agents; China; High-Throughput Nucleotide Sequencing; Humans; Mycoses; Talaromyces; Technology
PubMed: 36159645
DOI: 10.3389/fcimb.2022.987692 -
Pediatric Allergy and Immunology :... Oct 2021Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and...
BACKGROUND
Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline mutations in the TNFRSF6 gene. In this study, we conducted a systematic review of patients with ALPS and ALPS-like syndrome.
METHODS
The literature search was performed in Web of Science, Scopus, and PubMed databases to find eligible studies. Additionally, the reference list of all included papers was hand-searched for additional studies. Demographic, clinical, immunological, and molecular data were extracted and compared between the ALPS and ALPS-like syndrome.
RESULTS
Totally, 720 patients with ALPS (532 genetically determined and 189 genetically undetermined ALPS) and 59 cases with ALPS-like phenotype due to mutations in genes other than ALPS genes were assessed. In both ALPS and ALPS-like patients, splenomegaly was the most common clinical presentation followed by autoimmune cytopenias and lymphadenopathy. Among other clinical manifestations, respiratory tract infections were significantly higher in ALPS-like patients than ALPS. The immunological analysis showed a lower serum level of IgA, IgG, and lymphocyte count in ALPS-like patients compared to ALPS. Most (85%) of the ALPS and ALPS-like cases with determined genetic defects carry mutations in the FAS gene. About one-third of patients received immunosuppressive therapy with conventional or targeted immunotherapy agents. A small fraction of patients (3.3%) received hematopoietic stem cell transplantation with successful engraftment, and all except two patients survived after transplantation.
CONCLUSION
Our results showed that the FAS gene with 85% frequency is the main etiological cause of genetically diagnosed patients with ALPS phenotype; therefore, the genetic defect of the majority of suspected ALPS patients could be confirmed by mutation analysis of FAS gene.
Topics: Autoimmune Diseases; Autoimmune Lymphoproliferative Syndrome; Heterozygote; Humans; Lymphoproliferative Disorders; Mutation; Phenotype; fas Receptor
PubMed: 33963613
DOI: 10.1111/pai.13535 -
Journal of Travel Medicine Dec 2020Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines.
OBJECTIVES
Primary objectives of this review were (i) to determine the aetiology of fever in travellers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and (ii) to assess the predictors for specific tropical diseases.
METHOD
Embase, MEDLINE and Cochrane Library were searched with terms combining fever and travel/migrants. All studies focusing on causes of fever in returning travellers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses.
RESULTS
10 064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5-14, 3-11 and 5-7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants' characteristics, setting, laboratory investigations performed and diseases included.
CONCLUSION
Malaria accounted for one-fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travellers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-centre studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.
Topics: COVID-19; Communicable Disease Control; Diagnosis, Differential; Fever; Humans; Practice Guidelines as Topic; Transients and Migrants; Travel Medicine; Tropical Medicine
PubMed: 33146395
DOI: 10.1093/jtm/taaa207 -
Pediatric Pulmonology Feb 2020Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency disorder characterized by infectious and noninfectious complications.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency disorder characterized by infectious and noninfectious complications. Bronchiectasis continues to be a common respiratory problem and therapeutic challenge in CVID. The aim of this study is to estimate the overall prevalence of bronchiectasis and its associated phenotype in patients with CVID.
METHODS
A systematic literature search was performed in Web of Science, PubMed, and Scopus from the earliest available date to February 2019 with standard keywords. All pooled analyses of bronchiectasis prevalence and the corresponding 95% confidence intervals (CIs) were based on random-effects models.
RESULTS
Fifty-five studies comprising 8535 patients with CVID were included in the meta-analysis. Overall prevalence of bronchiectasis was 34% (95% CI: 30-38; I = 90.19%). CVID patients with bronchiectasis had significantly lower serum immunoglobulin A (IgA) and IgM levels at the time of diagnosis compared with those without bronchiectasis. Among the clinical features, the frequencies of splenomegaly, pneumonia, otitis media, and lymphocytic interstitial pneumonia were significantly higher in CVID patients with bronchiectasis compared with those without bronchiectasis, respectively.
CONCLUSION
A higher prevalence of bronchiectasis in patients with CVID should be managed by controlling recurrent and severe pneumonia episodes which are immune dysregulation since this complication is associated with poor prognosis in these patients.
Topics: Adult; Bronchiectasis; Common Variable Immunodeficiency; Female; Humans; Longitudinal Studies; Lung Diseases, Interstitial; Male; Otitis Media; Pneumonia; Prevalence
PubMed: 31833673
DOI: 10.1002/ppul.24599 -
Autopsy & Case Reports 2023Endocarditis is a rare, often fatal complication of rat bite fever caused by . Only 39 cases have been reported (including this case) as of 2022. We describe a case and...
INTRODUCTION
Endocarditis is a rare, often fatal complication of rat bite fever caused by . Only 39 cases have been reported (including this case) as of 2022. We describe a case and aim to perform this entit's first systematic literature review.
METHODS
We performed a systematic review in CENTRAL, EMBASE, MEDLINE, SciELO, and LILACS. The terms used were terms used were (but not limited to) rat bite fever, , and endocarditis. We included all abstracts and articles with patients with echocardiographic or histologic-proven endocarditis. In case of discordance, a third reviewer was involved. Our protocol was submitted to PROSPERO (CRD42022334092). We also performed searches for studies on the reference list of included articles.
RESULTS
We retrieved 108 and included 36 abstracts and articles. A total of 39 patients (including our report) were identified. The mean age was 41.27, and 61.5% were males. The most common findings were fever, murmur, arthralgias, fatigue, splenomegaly, and rash. Underlying heart disease was present in 33%. Exposure to rats was noted in 71.8% of patients, with 56.4% recalling a rat bite. Anemia was seen in 57%, leukocytosis in 52%, and elevated inflammatory markers in 58% that had lab work performed. The mitral valve was most affected, followed by the aortic, tricuspid, and pulmonary valves. Surgical intervention was required in 14 (36%) cases. Of those, 10 required valve replacement. Death was reported in 36% of cases. Unfortunately, the literature available is limited to case series and reports.
CONCLUSION
Our review allows clinicians to suspect better, diagnose, and manage Streptobacillary endocarditis.
PubMed: 37101553
DOI: 10.4322/acr.2023.423 -
Transplantation Reviews (Orlando, Fla.) Dec 2021Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include... (Review)
Review
INTRODUCTION
Portal vein obstruction (PVO) is a significant vascular complication after liver transplantation (LT) in pediatric patients. Current treatment strategies include percutaneous transluminal angioplasty (PTA), with or without stent placement, mesorex bypass (MRB), splenorenal shunt, mesocaval shunt, endovascular recanalization (EVR), splenic artery embolization and splenectomy. However, specific characteristics of patients undergoing intervention and selection of individual treatment and its efficacy have remained unclear. This review systematically analyzed biochemical and clinical characteristics, selection of treatment, efficacy, and post-procedural complications.
METHODS
We systematically searched PubMed and Embase between January 1995 and March 2021 for studies on the management of PVO after LT. We analyzed the reports for biochemical and clinical characteristics at the timing of the intervention in different patients, selection of treatment, and reported efficacies.
RESULTS
We found 22 cohort studies with 362 patients who had the following characteristics: biliary atresia (83%), living-donor LT (85%), thrombocytopenia (73%), splenomegaly (40%), ascites (16%), or gastrointestinal bleeding (26%). The 3-year primary patency of PTA without stent placement was similar to that with stent placement (70%-80% and 43%-94%, respectively). MRB was used as an initial treatment with a 3-year patency of 75% to 100%. One study showed that 5-year primary patency of EVR was 80%. Secondary patency was 90% to 100% after 3 years in all studies with PTA alone, PTA/stent placement, and stent placement alone.
CONCLUSION
This is the first review of all treatment protocols in PVO after pediatric LT. We showed that an important group of patients has severe symptoms of portal hypertension. Efficacy of all treatment modalities was high in the included studies which make them important modalities for these patients.
Topics: Angioplasty; Child; Humans; Liver Transplantation; Portal Vein; Stents; Vascular Patency
PubMed: 34107368
DOI: 10.1016/j.trre.2021.100630 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Molecular Genetics & Genomic Medicine Mar 2024Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual... (Review)
Review
BACKGROUND
Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS
We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS
We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSION
We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
Topics: Adult; Female; Humans; Asian People; Databases, Factual; Genotype; Intellectual Disability; Phenotype
PubMed: 38444259
DOI: 10.1002/mgg3.2398 -
Frontiers in Genetics 2022Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease,...
Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease, pancreatitis and/or multiple organ failures before diagnosis. Better guidelines for the recognition and early diagnosis of rare dyslipidaemias are urgently required. Genomic DNA was isolated from blood samples of a Pakistani paediatric patient with hypertriglyceridemia, and from his parents and siblings. Next-generation sequencing (NGS) was performed, and an expanded dyslipidaemia panel was employed for genetic analysis. The NGS revealed the presence of a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the (glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) gene resulting in amino acid change p.Cys77Tyr (NP_835466.2). The patient was 5.5 years old at the time of genetic diagnosis. The maximal total cholesterol and triglyceride levels were measured at the age of 10 months (850.7 mg/dl, 22.0 mmol/L and 5,137 mg/dl, 58.0 mmol/L, respectively). The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the gene and clinical findings, associated with hyperlipoproteinemia. In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the gene causing hyperlipoproteinemia (type 1D). In cases of severe elevations of plasma cholesterol and/or triglycerides genetic testing for rare dyslipidaemias should be performed as soon as possible for optimal therapy and patient management.
PubMed: 36051701
DOI: 10.3389/fgene.2022.983283