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Parkinsonism & Related Disorders Nov 2021This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively...
This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries. Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.
Topics: Asia; Asian People; Disease Management; Genetic Testing; Health Services Accessibility; Healthcare Disparities; Humans; Income; Phenotype; Prevalence; Spinocerebellar Ataxias
PubMed: 34711523
DOI: 10.1016/j.parkreldis.2021.10.023 -
Neuroepidemiology 2022Myotonic dystrophy (DM), the most common muscular dystrophy in adults, is a group of autosomal inherited neuromuscular disorders characterized by progressive muscle... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Myotonic dystrophy (DM), the most common muscular dystrophy in adults, is a group of autosomal inherited neuromuscular disorders characterized by progressive muscle weakness, myotonia, and cardiac conduction abnormalities. Due to the different gene mutations, DM has been subclassified into DM type 1 (DM1) and type 2 (DM2). However, the prevalence studies on DM and its subtypes are insufficient.
METHODS
The PubMed (1966-2022), MEDLINE (1950-2022), Web of Science (1864-2022), and Cochrane Library (2022) databases were searched for original research articles published in English. The quality of the included studies was assessed by a checklist adapted from Strengthening the Reporting of Observational studies in Epidemiology. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random-effects model. Heterogeneity was assessed using the Cochrane Q statistic and the I2 statistic.
RESULTS
A total of 17 studies were included in the systematic review and meta-analysis. Of the 17 studies evaluated, 14 studies were considered medium quality, 2 studies were considered high quality, and 1 study was considered low quality. The global prevalence of DM varied widely from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM was 9.99 cases (95% CI: 5.62-15.53) per 100,000. The pooled estimate of the prevalence of DM1 was 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM2 was 2.29 cases (95% CI: 0.17-6.53) per 100,000, ranging from 0.00 to 24.00 cases per 100,000.
CONCLUSION
Our study provided accurate estimates of the prevalence of DM. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher quality studies on orphan diseases.
Topics: Adult; Humans; Myotonic Dystrophy; Prevalence
PubMed: 35483324
DOI: 10.1159/000524734 -
RMD Open Jul 2020Several therapies are used for the treatment of rareautoinflammatory conditions like cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome... (Meta-Analysis)
Meta-Analysis
Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome.
OBJECTIVES
Several therapies are used for the treatment of rareautoinflammatory conditions like cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome (HIDS)/mevalonate kinase deficiency (MKD) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS). However, reviews reporting on treatment outcomes of these therapies are lacking.
METHODS
A systematic literature review was conducted using Embase, MEDLINE, MEDLINE-In Process and Cochrane databases to identify the randomised/non-randomised controlled trials (RCTs/non-RCTs) and real-world observational studies of CAPS, HIDS/MKD and TRAPS published as full-texts (January 2000-September 2017) or conference abstracts (January 2014-September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded.
RESULTS
Of the 3 342 retrieved publications, 72 studies were included (CAPS, n=43; HIDS/MKD, n=9; TRAPS, n=7; studies with ≥2 cohorts, n=13). Most studies were full-text (n=56), published after 2010 (n=56) and real-world observational studies (n=58). Among included studies, four were RCTs (canakinumab, n=2 (CAPS, n=1; HIDS/MKD and TRAPS, n=1); rilonacept, n=1 (in CAPS); simvastatin, n=1 (in HIDS/MKD)). Canakinumab and anakinra were the most commonly used therapies for CAPS and HIDS/MKD, whereas etanercept, canakinumab and anakinra were the most common for TRAPS. The available evidence suggested the efficacy or effectiveness of canakinumab and anakinra in CAPS, HIDS/MKD and TRAPS, and of etanercept in TRAPS; asingle RCT demonstrated the efficacy of rilonacept in CAPS.
CONCLUSIONS
Canakinumab, anakinra, etanercept and rilonacept were reported to be well tolerated; however, injection-site reactions were observed frequently with anakinra, rilonacept and etanercept. Data on the use of tocilizumab, infliximab and adalimumab in these conditions were limited; thus, further research is warranted.
Topics: Clinical Decision-Making; Combined Modality Therapy; Cryopyrin-Associated Periodic Syndromes; Disease Management; Disease Susceptibility; Drug Substitution; Fever; Hereditary Autoinflammatory Diseases; Humans; Mevalonate Kinase Deficiency; Publication Bias; Treatment Outcome
PubMed: 32723831
DOI: 10.1136/rmdopen-2020-001227 -
Journal of the Korean Association of... Aug 2020Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder. These patients lose their teeth at a young age and are in need of prosthetic rehabilitation. The... (Review)
Review
OBJECTIVES
Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder. These patients lose their teeth at a young age and are in need of prosthetic rehabilitation. The aim of this systematic review was to assess the success of dental implant placement in these patients.
MATERIALS AND METHODS
An electronic search was performed in PubMed Central, Scopus, and Web of Science using the keyword "Papillon-Lefèvre syndrome" AND "dental implant" OR "prosthodontics". Articles reporting implant placement in patients with PLS until July 2019 were included.
RESULTS
Assessment of the included 11 articles reporting 15 cases showed 136 implant placements in these patients. Implant failure occurred in 3 patients (20 implants). The peri-implantitis and failure rate was higher in the maxilla. Meta-analysis showed the probability of failure to be 7% (95% confidence interval [CI] 0%-31%) for maxillary implants and 2% (95% CI 0%-9%) for mandibular implants. The follow-up time ranged between 1 and 20 years. Healing after bone graft and implant placement in these patients was uneventful.
CONCLUSION
Dental implants may be a viable treatment option for PLS patients. Implantation can help preserve alveolar bone if the patients' immunological and growing conditions are well-considered and proper oral hygiene and compliance with the maintenance program are continued.
PubMed: 32855368
DOI: 10.5125/jkaoms.2020.46.4.220 -
International Journal of Molecular... Jul 2021CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in that lead to an... (Review)
Review
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor β (TGFβ) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets.
Topics: CADASIL; Cysteine; Gastrointestinal Microbiome; Gene Frequency; Gene Ontology; Genetic Association Studies; Genome-Wide Association Study; Genomics; Humans; Models, Molecular; Mutation; Nerve Tissue Proteins; Prevalence; Prognosis; Protein Aggregation, Pathological; Protein Conformation; Protein Domains; Proteomics; Receptor, Notch3; Sequence Analysis, DNA; Transcriptome
PubMed: 34298974
DOI: 10.3390/ijms22147357 -
The Cochrane Database of Systematic... Nov 2019Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops as a consequence of copper accumulating in affected tissues. There is no gold standard for the diagnosis of Wilson's disease, which is often delayed due to the non-specific clinical features and the need for a combination of clinical and laboratory tests for diagnosis. This delay may in turn affect clinical outcome and has implications for other family members in terms of diagnosis. The Leipzig criteria were established to help standardise diagnosis and management. However, it should be emphasised that these criteria date from 2003, and many of these have not been formally evaluated; this review examines the evidence behind biochemical testing for Wilson's disease.
OBJECTIVES
To determine the diagnostic accuracy of three biochemical tests at specified cut-off levels for Wilson's disease. The index tests covered by this Cochrane Review are caeruloplasmin, 24-hour urinary copper and hepatic copper content. These tests were evaluated in those with suspected Wilson's disease and appropriate controls (either healthy or those with chronic liver disease other than Wilson's). In the absence of a gold standard for diagnosing Wilson's disease, we have used the Leipzig criteria as a clinical reference standard. To investigate whether index tests should be performed in all individuals who have been recommended for testing for Wilson's disease, or whether these tests should be limited to subgroups of individuals.
SEARCH METHODS
We identified studies by extensive searching of, e.g. the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Web of Science and clinical trial registries (29 May 2019). Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Inborn Errors of Metabolism Register: 29 May 2019.
SELECTION CRITERIA
We included prospective and retrospective cohort studies that assessed the diagnostic accuracy of an index test using the Leipzig criteria as a clinical reference standard for the diagnosis of Wilson's disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data and assessed the methodological quality of each included study using the QUADAS-2 tool. We had planned to undertake meta-analyses of the sensitivity, specificity at relevant cut-offs for each of the biochemical tests for Wilson's, however, due to differences in the methods used for each biochemical index test, it was not possible to combine the results in meta-analyses and hence these are described narratively.
MAIN RESULTS
Eight studies, involving 5699 participants (which included 1009 diagnosed with Wilson's disease) were eligible for inclusion in the review. Three studies involved children only, one adults only and the four remaining studies involved both children and adults. Two evaluated participants with hepatic signs and six with a combination of hepatic and neurological signs and symptoms of Wilson's disease, as well as pre-symptomatic individuals. The studies were of variable methodological quality; with high risk if bias for participant selection and the reference standard used being of greatest methodological concern. Key differences between studies include differences in assay methodology, different cut-off values for diagnostic thresholds, different age and ethnicity groups. Concerns around study design imply that diagnostic accuracy figures may not transfer to populations outside of the relevant study.
INDEX TEST
caeruloplasmin Five studies evaluated various thresholds of caeruloplasmin (4281 participants, of which 541 had WD). For caeruloplasmin a cut-off of 0.2 g/L as in the Leipzig criteria achieved a sensitivity of 77.1% to 99%, with variable specificity of 55.9% to 82.8%. Using the cut-off of 0.1 g/L of the Leipzig criteria seemed to lower the sensitivity overall, 65% to 78.9%, while increasing the specificity to 96.6% to 100%.
INDEX TEST
hepatic copper Four studies evaluated various thresholds of hepatic copper (1150 participants, of which 367 had WD). The hepatic copper cut-off of 4 μmol/g used in the Leipzig criteria achieved a sensitivity of 65.7% to 94.4%, with a variable specificity of 52.2% to 98.6%.
INDEX TEST
24-hour urinary copper Three studies evaluated various thresholds of 24-hour urinary copper (268 participants, of which 101 had WD). For 24-hour urinary copper, a cut-off of 0.64 to 1.6 μmol/24 hours used in the Leipzig criteria achieved a variable sensitivity of 50.0% to 80.0%, with a specificity of 75.6% to 98.3%.
AUTHORS' CONCLUSIONS
The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used. Binary cut-offs and use of single-test strategies to rule Wilson's disease in or out is not supported by the evidence in this review. There is insufficient evidence to inform testing in specific subgroups, defined by age, ethnicity or clinical subgroups.
Topics: Biomarkers; Ceruloplasmin; Copper; Hepatolenticular Degeneration; Humans; Liver; Randomized Controlled Trials as Topic
PubMed: 31743430
DOI: 10.1002/14651858.CD012267.pub2 -
Journal of Clinical Sleep Medicine :... Feb 2020Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism resulting in pathologic accumulation of copper in many organs and tissues. Sleep... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism resulting in pathologic accumulation of copper in many organs and tissues. Sleep disorders are highly prevalent in patients with WD. However, both prevalence rates and severity of different sleep disorders in patients with WD vary widely. The aims of the current study were to systematically review and perform a meta-analysis of the association between WD and prevalent sleep disorders, including insomnia, rapid eye movement (REM) sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), sleep-disordered breathing (SDB), restless legs syndrome (RLS), periodic limb movement in sleep (PLM), cataplexy-like episodes (CLEs) and sleep paralysis, and objective sleep characteristics.
METHODS
We performed a systematic search of PubMed, EMBase, the Cochrane Library, PsycINFO and ISI Web of Science for case-control studies. A total of 7 studies with 501 participants were included.
RESULTS
We found that 54.1% of patients with WD experience sleep disorders and up to 7.65-fold higher odds compared to control patients. Specifically, patients with WD had higher rates of RBD, insomnia, and EDS based on self-reported questionnaires. No differences were observed in terms of RLS, PLM, or SDB between patients with WD and control patients. Furthermore, objective sleep disruptions based on polysomnographic studies included prolonged sleep onset latency and REM sleep onset latency, reduced total sleep time and sleep efficiency, higher percentage of stage N1 sleep and lower percentage of stage N2 sleep were observed in patients with WD.
CONCLUSIONS
Our study indicates that sleep disorders are frequent in patients with WD. Future studies should examine the longitudinal association of WD with sleep disturbances.
Topics: Disorders of Excessive Somnolence; Hepatolenticular Degeneration; Humans; Polysomnography; REM Sleep Behavior Disorder; Restless Legs Syndrome; Sleep Wake Disorders
PubMed: 31992405
DOI: 10.5664/jcsm.8170 -
Ultrasound in Obstetrics & Gynecology :... Jan 2021To determine the incremental yield of antenatal exome sequencing (ES) over chromosomal microarray analysis (CMA) or conventional karyotyping in prenatally diagnosed...
OBJECTIVE
To determine the incremental yield of antenatal exome sequencing (ES) over chromosomal microarray analysis (CMA) or conventional karyotyping in prenatally diagnosed congenital heart disease (CHD).
METHODS
A prospective cohort study of 197 trios undergoing ES following CMA or karyotyping owing to CHD identified prenatally and a systematic review of the literature were performed. MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov (January 2000 to October 2019) databases were searched electronically for studies reporting on the diagnostic yield of ES in prenatally diagnosed CHD. Selected studies included those with more than three cases, with initiation of testing based upon prenatal phenotype only and that included cases in which CMA or karyotyping was negative. The incremental diagnostic yield of ES was assessed in: (1) all cases of CHD; (2) isolated CHD; (3) CHD associated with extracardiac anomaly (ECA); and (4) CHD according to phenotypic subgroup.
RESULTS
In our cohort, ES had an additional diagnostic yield in all CHD, isolated CHD and CHD associated with ECA of 12.7% (25/197), 11.5% (14/122) and 14.7% (11/75), respectively (P = 0.81). The corresponding pooled incremental yields from 18 studies (encompassing 636 CHD cases) included in the systematic review were 21% (95% CI, 15-27%), 11% (95% CI, 7-15%) and 37% (95% CI, 18-56%), respectively. The results did not differ significantly when subanalysis was limited to studies including more than 20 cases, except for CHD associated with ECA, in which the incremental yield was greater (49% (95% CI, 17-80%)). In cases of CHD associated with ECA in the primary analysis, the most common extracardiac anomalies associated with a pathogenic variant were those affecting the genitourinary system (23/52 (44.2%)). The greatest incremental yield was in cardiac shunt lesions (41% (95% CI, 19-63%)), followed by right-sided lesions (26% (95% CI, 9-43%)). In the majority (68/96 (70.8%)) of instances, pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease genes. The most common (19/96 (19.8%)) monogenic syndrome identified was Kabuki syndrome.
CONCLUSIONS
There is an apparent incremental yield of prenatal ES in CHD. While the greatest yield is in CHD associated with ECA, consideration could also be given to performing ES in the presence of an isolated cardiac abnormality. A policy of routine application of ES would require the adoption of robust bioinformatic, clinical and ethical pathways. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Female; Heart Defects, Congenital; Humans; Karyotyping; Microarray Analysis; Pregnancy; Prenatal Diagnosis; Prospective Studies; Exome Sequencing
PubMed: 32388881
DOI: 10.1002/uog.22072 -
The Cochrane Database of Systematic... Mar 2020Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. This is an updated version of a previously published review.
OBJECTIVES
To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.
SELECTION CRITERIA
Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS
Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS
A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS
In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
Topics: Adult; Child; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Diseases; Randomized Controlled Trials as Topic
PubMed: 32227478
DOI: 10.1002/14651858.CD012056.pub3 -
Chromosoma Sep 2022Chromosomal translocations (CTs) are the most common type of structural chromosomal abnormalities in humans. CTs have been reported in several studies in the Arab world,... (Review)
Review
Chromosomal translocations (CTs) are the most common type of structural chromosomal abnormalities in humans. CTs have been reported in several studies in the Arab world, but the frequency and spectrum of these translocations are not well characterized. The aim of this study is to conduct a systematic review to estimate the frequency and spectrum of CTs in the 22 Arab countries. Four literature databases were searched: PubMed, Science Direct, Scopus, and Web of Science, from the time of inception until July 2021. A combination of broad search terms was used to collect all possible CTs reported in the Arab world. In addition to the literature databases, all captured CTs were searched in three chromosomal rearrangement databases (Mitelman Database, CytoD 1.0 Database, and the Atlas of Genetics and Cytogenetics in Oncology and Hematology), along with PubMed and Google Scholar, to check whether the CTs are unique to the Arabs or shared between Arabs and non-Arabs. A total of 9,053 titles and abstracts were screened, of which 168 studies met our inclusion criteria, and 378 CTs were identified in 15 Arab countries, of which 57 CTs were unique to Arab patients. Approximately 89% of the identified CTs involved autosomal chromosomes. Three CTs, t(9;22), t(13;14), and t(14;18), showed the highest frequency, which were associated with hematological malignancies, recurrent pregnancy loss, and follicular lymphoma, respectively. Complex CTs were commonly reported among Arabs, with a total of 44 CTs, of which 12 were unique to Arabs. This is the first study to focus on the spectrum of CTs in the Arab world and compressively map the ethnic-specific CTs relevant to cancer. It seems that there is a distinctive genotype of Arabs with CTs, of which some manifested with unique clinical phenotypes. Although ethnic-specific CTs are highly relevant to disease mechanism, they are understudied and need to be thoroughly addressed.
Topics: Arab World; Arabs; Female; Humans; Middle East; Phenotype; Pregnancy; Translocation, Genetic
PubMed: 35907041
DOI: 10.1007/s00412-022-00775-2