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Annals of Human Biology Jun 2021Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of...
CONTEXT
Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of mutations and the prevalence of thalassaemia, but findings are often contradictory.
OBJECTIVE
This systematic review aimed to provide a comprehensive view of the prevalence of thalassaemia-associated mutations in different countries, their effect on haemoglobin (Hb) levels, as well as reporting thalassaemia-associated rare mutations.
METHODS
A systematic search of the literature was carried out through major indexing databases (MEDLINE/PubMed, Scopus, EMBASE, Cochrane central, and ISI web of science) using keywords: "Co-inheritance, αα, β, thalassaemia" and "α-β thalassaemia, Mediterranean anemia, mutations" from 1998-September 2019. Hand-searching was also performed. There was no language restriction.
RESULTS
The initial searches yielded 1059 studies, of which 92 articles were included following inclusion and exclusion criteria. Of these, 3.3% (3) of articles were cohort studies, and 96.7% (89) of the remaining articles were cross-sectional studies. Our findings showed that 45.6% (42) of researchers investigated β-thalassaemia, 22.9% (21) αα-β thalassaemia, and 31.5% (29) α thalassaemia.
CONCLUSION
The present study provides valuable information about the spectrum of thalassaemia-associated mutations, which can be useful for preventing thalassaemia, reducing costs of care, reducing the treatment-related side effects, and showing the most defective mutations.HighlightEvaluating the increase or decrease in the birth prevalence of thalassaemiaIdentifying the most common and rare mutations in various parts of the worldComparing researchers' findings from various parts of the world.
Topics: Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 34032183
DOI: 10.1080/03014460.2021.1909135 -
Human Genetics Dec 2021ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to...
ATR-X, an acronym for alpha thalassemia and mental retardation X-linked, syndrome is a congenital condition predominantly affecting males, characterized by mild to severe intellectual disability, facial, skeletal, urogenital, and hematopoietic anomalies. Less common are heart defects, eye anomalies, renal abnormalities, and gastrointestinal dysfunction. ATR-X syndrome is caused by germline variants in the ATRX gene. Until recently, the diagnosis of the ATR-X syndrome had been guided by the classical clinical manifestations and confirmed by molecular techniques. However, our new systematic analysis shows that the only clinical sign shared by all affected individuals is intellectual disability, with the other manifestations varying even within the same family. More than 190 different germline ATRX mutations in some 200 patients have been analyzed. With improved and more frequent analysis by molecular technologies, more subtle deletions and insertions have been detected recently. Moreover, emerging technologies reveal non-classic phenotypes of ATR-X syndrome as well as the description of a new clinical feature, the development of osteosarcoma which suggests an increased cancer risk in ATR-X syndrome. This review will focus on the different types of inherited ATRX mutations and their relation to clinical features in the ATR-X syndrome. We will provide an update of the frequency of clinical manifestations, the affected organs, and the genotype-phenotype correlations. Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Topics: Animals; Humans; Intellectual Disability; Mental Retardation, X-Linked; Molecular Diagnostic Techniques; Mutation; alpha-Thalassemia
PubMed: 34524523
DOI: 10.1007/s00439-021-02361-5 -
The Cochrane Database of Systematic... Nov 2016Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of... (Review)
Review
BACKGROUND
Thalassemia is an inherited autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions. This results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their destruction (haemolysis) and ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the curative potential. This is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 18 August 2016.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane methodologies but no studies were identified for inclusion.
MAIN RESULTS
No relevant studies were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 27900772
DOI: 10.1002/14651858.CD008708.pub4 -
International Journal of Molecular... May 2024Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical... (Review)
Review
Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while variants were protective against albuminuria alone. The long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (, , and ) and nine loci were linked with eGFR (, , , , , , , , and ). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.
Topics: Humans; Anemia, Sickle Cell; Genome-Wide Association Study; Genetic Predisposition to Disease; Kidney Diseases; Apolipoprotein L1; Disease Progression; Genes, Modifier; Glomerular Filtration Rate
PubMed: 38791464
DOI: 10.3390/ijms25105427 -
American Journal of Obstetrics and... Mar 2015We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSDs) in case series of nonimmune hydrops (NIH).... (Review)
Review
We performed a systematic review of the literature to evaluate the incidence and types of lysosomal storage disorders (LSDs) in case series of nonimmune hydrops (NIH). PubMed and Ovid were reviewed for case series evaluating the workup of NIH diagnosed in utero or in the neonatal period in human subjects. Search terms were as follows: nonimmune hydrops, non immune hydrops, metabolic genetic disorders, and lysosomal storage disorders. The time period searched was 1979 through January 2014. Retrospective case series with at least 5 cases of fetal and/or neonatal NIH with its workup mentioned were identified. Idiopathic NIH was defined as NIH without an apparent cause after an initial workup. Exclusion criteria included studies published in languages other than English and review articles. The 3 authors screened all abstracts and manuscripts independently. Metaanalysis of Observational Studies in Epidemiology guidelines were followed. Fifty-four case series with 678 total cases of NIH were identified. The overall incidence of LSD was 5.2% (35 of 678) in all NIH cases that tested for any LSD and 17.4% (35 of 201) in idiopathic NIH cases. The 3 most common LSDs identified in cases of NIH, in order of decreasing incidence, were Mucopolysaccharidosis type VII, Gaucher's disease, and GM1-gangliosidosis. LSDs occur in 5.2% of all NIH cases and in 17.4% of idiopathic NIH cases and so should be screened for in this clinical scenario. Additionally, if a comprehensive LSD workup is completed on idiopathic cases, 29.6% of those would be reclassified as LSD. LSD testing does not only allow diagnosis but also ensures better counseling, appropriate management, and planning for possible early intervention. Moreover, their detection may aid in a prenatal diagnosis in subsequent pregnancies.
Topics: Female; Humans; Hydrops Fetalis; Lysosomal Storage Diseases; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 25305402
DOI: 10.1016/j.ajog.2014.10.007 -
Arquivos Brasileiros de Cardiologia Dec 2022Sickle cell anemia (SCA) is a hereditary disease whose cardiovascular complications are the main cause of death, the same being observed in other hemoglobinopathies....
BACKGROUND
Sickle cell anemia (SCA) is a hereditary disease whose cardiovascular complications are the main cause of death, the same being observed in other hemoglobinopathies. Early identification of these changes can favorably modify the course of the disease.
OBJECTIVE
To compare the prevalence of cardiovascular complications between individuals with SCA and individuals with other hemoglobinopathies.
METHOD
Following the recommendations of the PRISMA protocol, a systematic literature review was carried out with searches in PubMed/Medline databases, associated with a manual search. Studies that analyzed the prevalence of cardiovascular alterations in hemoglobinopathies (SCA, sickle cell trait, SC hemoglobinopathy, alpha-thalassemia and beta-thalassemia) were included. The methodological quality of the articles was assessed using the Newcastle-Ottawa scale.
RESULTS
Four studies were selected for analysis, resulting in a sample size of 582 participants: 289 with SCA, 133 with SC hemoglobinopathy, 40 with beta-thalassemia, 100 healthy individuals and none with alpha-thalassemia or sickle cell trait. Dilatation of the cardiac chambers, left and right ventricular hypertrophy, pulmonary hypertension, diastolic dysfunction, mitral regurgitation and tricuspid regurgitation are more prevalent in SCA than in the other hemoglobinopathies considered. Myocardial iron overload is more frequent in thalassemia major than in sickle cell anemia. Systolic function is similar between different hemoglobinopathies.
CONCLUSION
There is greater cardiovascular impairment in individuals with SCA than in those with other hemoglobinopathies, reinforcing the necessity for regular cardiovascular follow-up in sickle cell patients.
Topics: Humans; beta-Thalassemia; Sickle Cell Trait; alpha-Thalassemia; Prevalence; Hemoglobinopathies; Anemia, Sickle Cell
PubMed: 36417618
DOI: 10.36660/abc.20220207 -
Prenatal Diagnosis Sep 2017The purpose of this systematic review is to provide a comprehensive overview on the clinical course, perinatal outcome, and effectiveness of prenatal management options... (Review)
Review
OBJECTIVES
The purpose of this systematic review is to provide a comprehensive overview on the clinical course, perinatal outcome, and effectiveness of prenatal management options for pericardial teratoma.
METHODS
A comprehensive search including Ovid MEDLINE, Ovid EMBASE, and Scopus was conducted from inception to September 2016. All studies that reported the prenatal course of pericardial teratoma in singleton or twin gestations were considered eligible. Standardized forms were used for data abstraction by two independent reviewers.
RESULTS
Out of 217 screened abstracts, 59 studies reporting 67 fetuses with pericardial teratoma were included. Twenty-three singleton fetuses and 3 fetuses in twin gestations underwent prenatal treatment, and 20 (76.9%) of them were hydropic at the time of intervention. Of those, 15/20 (75%) had a favorable outcome. In the non-intervention group (n = 41), 26 (63.4%) developed hydrops, and out of those, 8 (30.8%) had a favorable outcome.
CONCLUSION
Prenatal fluid drainage and other prenatal techniques have been utilized in the treatment of intrapericardial teratoma. While most fetuses tolerated pericardiocentesis, the neonatal benefit of this procedure is still uncertain, and outcomes of other interventions had variable success. Prenatal intervention for pericardial teratoma may be an option in specialized units but, given the maternal and fetal risks, needs careful consideration. © 2017 John Wiley & Sons, Ltd.
Topics: Diseases in Twins; Drainage; Female; Fetal Diseases; Fetal Heart; Heart Neoplasms; Humans; Hydrops Fetalis; MEDLINE; Male; Pericardium; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Risk Factors; Teratoma
PubMed: 28695637
DOI: 10.1002/pd.5113 -
The Cochrane Database of Systematic... Oct 2014Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate... (Review)
Review
BACKGROUND
Thalassemia is an inherited blood disorder, caused by mutations in regulatory genes and transmitted as an autosomal recessive disorder, which results in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In ß-thalassaemia major there is an underproduction of ß-globin chains combined with excess of free α-globin chains. The excess free α-globin chains damage the red blood cell membranes, leading to their destruction and a phenomenon termed ineffective erythropoiesis. The conventional approach to treatment is based on the correction of haemoglobin status through regular blood transfusions and iron chelation therapy for iron overload. Although conventional treatment has the capacity to improve the quality of life of people with ß-thalassaemia major, allogeneic hematopoietic stem cell transplantation is the only currently available procedure which has the potential to definitively cure the disease.
OBJECTIVES
To evaluate the effectiveness and safety of different types of allogeneic hematopoietic stem cell transplantation, in people with severe transfusion-dependant ß-thalassaemia major, ß-thalassaemia intermedia or ß0/+- thalassaemia variants requiring chronic blood transfusion.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 11 November 2013.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing allogeneic hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies and had planned to extract data and assess risk of bias using standard Cochrane Collaboration methodologies but no studies were identified for inclusion.
MAIN RESULTS
No relevant studies were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of allogeneic stem cell transplantation in people with severe transfusion-dependant ß-thalassaemia major or ß0/+- thalassaemia variants requiring chronic blood transfusion. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 25316103
DOI: 10.1002/14651858.CD008708.pub3 -
Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557 -
The Cochrane Database of Systematic... Apr 2021Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one...
BACKGROUND
Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate the effectiveness and safety of different types of hematopoietic stem cell transplantation, in people with transfusion-dependent β-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of the most recent search: 07 April 2021.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing hematopoietic stem cell transplantation with each other or with standard therapy (regular transfusion and chelation regimen).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials and had planned to extract data and assess risk of bias using standard Cochrane methodologies and assess the quality using GRADE approach, but no trials were identified for inclusion in the current review.
MAIN RESULTS
No relevant trials were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled trials or quasi-randomised controlled trials on the effectiveness and safety of different types of hematopoietic stem cell transplantation in people with transfusion-dependent β-thalassaemia. The absence of high-level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately-powered, randomised controlled clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; beta-Thalassemia
PubMed: 33880750
DOI: 10.1002/14651858.CD008708.pub5