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Leukemia Research Dec 2021
Topics: Genetic Diseases, X-Linked; Humans; Myelodysplastic Syndromes; Myeloproliferative Disorders; alpha-Thalassemia
PubMed: 34325177
DOI: 10.1016/j.leukres.2021.106670 -
The Journal of Maternal-fetal &... Oct 2022Mirror syndrome is a rare disease associated with high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often associated with preeclampsia.... (Review)
Review
INTRODUCTION
Mirror syndrome is a rare disease associated with high fetal mortality of up to 67.2%. It is thought to be underdiagnosed and is often associated with preeclampsia. Mirror syndrome is characterized by "triple edema": generalized maternal, placental, and fetal edema.
OBJECTIVE
This comprehensive review aims to thoroughly summarize the existing data and provide a broad update on the topic to help accurate diagnosis and encourage further research.
METHODS
A comprehensive search of several databases (Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) was conducted.
RESULTS
The last systematic review of mirror syndrome cases was conducted in 2016 and included 113 patients. Much is still unknown about the pathophysiology of the disease and it remains underdiagnosed.
CONCLUSIONS AND RELEVANCE
Mirror syndrome is likely more prevalent than current data suggests for it is often misdiagnosed as pre-eclampsia. The differential of Mirror syndrome should be considered in anomalous presentations of pre-eclampsia as intervention may save the fetus and improve maternal symptoms. It is important to further the study on the pathophysiology of the disease to better understand, diagnose and potentially treat it, to avoid its high morbidity and mortality.
Topics: Edema; Female; Humans; Hydrops Fetalis; Placenta; Pre-Eclampsia; Pregnancy; Syndrome; Systematic Reviews as Topic
PubMed: 33722118
DOI: 10.1080/14767058.2020.1844656 -
Clinical Genetics May 2023Non-immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the... (Meta-Analysis)
Meta-Analysis Review
Non-immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty-one studies reporting 445 NIHF cases had a 37% (95% CI: 32%-41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non-consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X-linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity.
Topics: Pregnancy; Female; Humans; Hydrops Fetalis; Exome Sequencing; Consanguinity
PubMed: 36757664
DOI: 10.1111/cge.14309 -
Molecular Genetics and Genomics : MGG Jan 2023The CRISPR/Cas9 technique is easily programmable, fast, more powerful, and efficient at generating a mutation compared to previous gene therapy methods. β-thalassemia... (Review)
Review
The CRISPR/Cas9 technique is easily programmable, fast, more powerful, and efficient at generating a mutation compared to previous gene therapy methods. β-thalassemia is the most common autosomal recessive disorder worldwide. Appropriate genomic changes in the β gene can be modified to alleviate the symptoms of the disease using the CRISPR/Cas9 system. PubMed/Medline, Scopus, Web of Science, and SID databases were searched in Persian and English from February 2000 to September 2022. Finally, 39 articles had inclusion criteria which were reviewed by two separate individuals. Among the reviewed articles, articles were divided into three categories. In the first group, studies attemped to increase the expression of γ-globin and production of hemoglobin F. The strategy of second group of studies were the reduction of the α-globin chain to prevent hemolysis of RBCs by accumulation of excessive α-globins. The third group corrected the mutations causing β-thalassemia. Studies have shown that the genome of β-thalassemia patients can be modified using the CRISPR/Cas9 technique, and this approach might be promising for the treatment of β-thalassemia.
Topics: Humans; CRISPR-Cas Systems; Gene Editing; beta-Thalassemia; Mutation
PubMed: 36403178
DOI: 10.1007/s00438-022-01978-z -
Frontiers in Medicine 2022β-thalassemia is a disease caused by genetic mutations including a nucleotide change, small insertions or deletions in the β-globin gene, or in rare cases, gross...
β-thalassemia is a disease caused by genetic mutations including a nucleotide change, small insertions or deletions in the β-globin gene, or in rare cases, gross deletions into the β-globin gene. These mutations affect globin-chain subunits within the hemoglobin tetramer what induces an imbalance in the α/β-globin chain ratio, with an excess of free α-globin chains that triggers the most important pathogenic events of the disease: ineffective erythropoiesis, chronic anemia/chronic hypoxia, compensatory hemopoietic expansion and iron overload. Based on advances in our knowledge of the pathophysiology of β-thalassemia, in recent years, emerging therapies and clinical trials are being conducted and are classified into three major categories based on the different approach features of the underlying pathophysiology: correction of the α/β-globin disregulation; improving iron overload and reverse ineffective erythropoiesis. However, pathways such as the dysregulation of transcriptional factors, activation of the inflammasome, or approach to mechanisms of bone mineral loss, remain unexplored for future therapeutic targets. In this review, we update the main pathophysiological pathways involved in β-thalassemia, focusing on the development of new therapies directed at new therapeutic targets.
PubMed: 35492364
DOI: 10.3389/fmed.2022.880752 -
Reviews on Recent Clinical Trials May 2024β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
BACKGROUND
β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
OBJECTIVE
This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on β-thalassemia outcomes in children and adolescents.
METHODS
A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety.
RESULTS
By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects.
CONCLUSION
Silymarin indicates promising effects on various aspects of children and adolescents with β-thalassemia and has no serious side effects on the investigated dosage.
PubMed: 38818907
DOI: 10.2174/0115748871305325240511122602 -
Hematology (Amsterdam, Netherlands) Dec 2019Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various...
OBJECTIVES
Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease.
METHODS
A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease.
RESULTS
Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators.
DISCUSSION AND CONCLUSION
Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.
Topics: Female; Humans; Hypoxia; Iron Overload; Kidney Diseases; Male; beta-Thalassemia
PubMed: 30947625
DOI: 10.1080/16078454.2019.1599096 -
Prenatal Diagnosis Dec 2016Alpha thalassemia major (ATM) is often fatal in utero due to severe hydrops fetalis. Although in utero transfusions (IUTs) are increasingly used to allow fetal survival... (Review)
Review
OBJECTIVE
Alpha thalassemia major (ATM) is often fatal in utero due to severe hydrops fetalis. Although in utero transfusions (IUTs) are increasingly used to allow fetal survival in ATM, prenatal and postnatal outcomes are not well described.
METHODS
We retrospectively reviewed cases of ATM at our institution treated with consecutive IUT. Clinical records were reviewed for transfusion history, neurodevelopmental outcomes, anatomic abnormalities, survival to hematopoietic cell transplantation, and transfusion independence. A systematic review was performed, and additional reported cases are discussed.
RESULTS
Three patients who underwent IUT for ATM were identified, and review of the literature revealed 17 reported cases. Of patients who received IUT, reported neurodevelopmental deficits occurred in 29% (4/14) and anatomic abnormalities in 55% (11/20). Four patients eventually underwent successful hematopoietic cell transplantation. Transfusion volumes were less than suggested guidelines for other causes of fetal anemia in 91.7% of the transfusions.
CONCLUSION
This series demonstrates the potential for achieving full fetal development with normal neurologic outcomes in those affected by ATM. It provides support for continued patient and provider education about current benefits and risks of active prenatal therapy for fetuses with ATM, as well as continued research to optimize therapeutic strategies such as in utero transplantation. © 2016 John Wiley & Sons, Ltd.
Topics: Blood Transfusion, Intrauterine; Female; Fetal Development; Fetal Diseases; Follow-Up Studies; Gestational Age; Hematopoietic Stem Cell Transplantation; Humans; Hydrops Fetalis; Male; Neurodevelopmental Disorders; Pregnancy; Pregnancy Outcome; Treatment Outcome; alpha-Thalassemia
PubMed: 27862048
DOI: 10.1002/pd.4966 -
The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
Blood Cells, Molecules & Diseases Jun 2017All patients with HbSS (SCA) share the same genetic mutation but the clinical phenotype is variable and difficult to predict early in life. A reliable severity predictor... (Meta-Analysis)
Meta-Analysis Review
All patients with HbSS (SCA) share the same genetic mutation but the clinical phenotype is variable and difficult to predict early in life. A reliable severity predictor would be invaluable toward directing therapeutic decisions in those patients at highest risk of SCA complications. A search of PubMed, Cochrane Clinical Trials Register, and Scopus was performed to determine which SCA severity predictors have been validated in pediatric patients. The full text of 94 of the 590 references identified was reviewed based on the title/abstract. Fifty-four articles were included in the analysis. Alpha globin gene number was the most commonly studied severity predictor, followed by fetal hemoglobin (HbF) and reticulocyte count. Alpha thalassemia trait was protective against overt stroke and abnormal transcranial Doppler (TCD) in all but one study, but not frequency of painful crisis or silent cerebral infarct. Two thirds of the HbF studies reported beneficial effects with increasing HbF levels; however, increased HbF levels were not associated with lower hospitalization or stroke rates in others. The ability to predict SCA complications was mixed for all variables, except TCD and absolute reticulocyte count. More reliable predictors are urgently needed to guide therapeutic decisions in children with SCA.
Topics: Anemia, Sickle Cell; Biomarkers; Child; Fetal Hemoglobin; Humans; Prognosis; Reticulocyte Count; Severity of Illness Index; alpha-Globins; beta-Globins
PubMed: 28185829
DOI: 10.1016/j.bcmd.2017.01.014