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Journal of Clinical Laboratory Analysis Jun 2021Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler...
BACKGROUND
Stroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha-thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha-thalassemia and G6PD(A ) variant with abnormal TCD velocities among Nigerian children with SCA.
METHODS
One hundred and forty-one children with SCA were recruited: 72 children presented with normal TCD (defined as the time-averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha-thalassemia (the α-3.7 globin gene deletion) was determined by multiplex gap-PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism-polymerase chain reaction.
RESULTS
The frequency of α-thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α-/ α α: 41.7%, α -/ α -: 11.1%] versus 21/69 (30.4%) [α-/ α α: 27.5%, α -/ α -: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α-thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20-0.78, p = 0.007]. However, the frequencies of G6PDA variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).
CONCLUSION
Our study reveals the protective role of α-thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
Topics: Adolescent; Anemia, Sickle Cell; Blood Flow Velocity; Case-Control Studies; Cerebrovascular Circulation; Child; Child, Preschool; Female; Follow-Up Studies; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Nigeria; Prognosis; Stroke; Ultrasonography, Doppler, Transcranial; alpha-Thalassemia
PubMed: 33938598
DOI: 10.1002/jcla.23802 -
Neuropediatrics Apr 2022This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.
BACKGROUND
This study explores the prevalence, clinical characteristics, and treatment of epilepsy and sleep disorders in α thalassemia mental retardation (ATR-X) syndrome.
DESIGN
In this cross-sectional study, 37 participants with ATR-X syndrome aged 1.8 to 44 years were studied using a customized epilepsy questionnaire, review of electroencephalography (EEG) findings, the modified Sleep Questionnaire of Simonds and Parraga and 2-week sleep diary.
RESULTS
Eleven participants had a clinical diagnosis of generalized epilepsy (29.7%). Seizure types were generalized tonic-clonic seizures, absences, and myoclonia. Interictal EEG recordings in participants with GTCS showed no epileptic discharges in 78%. Similarly, EEG recordings during myoclonia and absences often demonstrated no epileptic discharges. Sleep problems (difficulty falling or maintaining sleep, and early awakening) were reported in 70%. Participants with reported sleep problems went to bed earlier ( = 0.027) and had a lower sleep efficiency ( < 0.01) than participants without sleep problems, but as a group they both had a sufficient total sleep time (9 hours and 52 minutes vs. 10 hours and 55 minutes). Sixteen participants (43.2) used medication to improve sleep (predominantly melatonin = 10), being effective in only two.
CONCLUSION
One-third of participants with ATR-X syndrome had a clinical diagnosis of epilepsy, but the absence of EEG abnormalities in suspected epileptic seizures questions this diagnosis in these patients. EEG recording during seizure like symptoms is warranted before making an epilepsy diagnosis. Seventy percent experienced sleep problems, although total sleep time was normal in most participants. Long bedtimes might have a negative influence on sleep efficiency.
Topics: Ataxia Telangiectasia Mutated Proteins; Cross-Sectional Studies; Electroencephalography; Epilepsy; Epilepsy, Generalized; Humans; Mental Retardation, X-Linked; Myoclonus; Seizures; Sleep; Sleep Wake Disorders; alpha-Thalassemia
PubMed: 34933379
DOI: 10.1055/s-0041-1740551 -
International Journal of Molecular... Nov 2023The dADD1 and dXNP proteins are orthologues of the ADD and SNF2 domains of the vertebrate ATRX (Alpha-Thalassemia with mental Retardation X-related) protein. ATRX plays... (Review)
Review
The dADD1 and dXNP proteins are orthologues of the ADD and SNF2 domains of the vertebrate ATRX (Alpha-Thalassemia with mental Retardation X-related) protein. ATRX plays a role in general molecular processes, such as regulating chromatin status and gene expression, while dADD1 and dXNP have similar functions in the genome. Both ATRX and dADD1/dXNP interact with various protein partners and participate in various regulatory complexes. Disruption of ATRX expression in humans leads to the development of α-thalassemia and cancer, especially glioma. However, the mechanisms that allow ATRX to regulate various cellular processes are poorly understood. Studying the functioning of dADD1/dXNP in the model may contribute to understanding the mechanisms underlying the multifunctional action of ATRX and its connection with various cellular processes. This review provides a brief overview of the currently available information in mammals and regarding the roles of ATRX, dXNP, and dADD1. It discusses possible mechanisms of action of complexes involving these proteins.
Topics: Animals; Humans; alpha-Thalassemia; Chromatin; DNA Helicases; Drosophila; Drosophila melanogaster; Drosophila Proteins; Mammals; X-linked Nuclear Protein
PubMed: 38003676
DOI: 10.3390/ijms242216486 -
Orphanet Journal of Rare Diseases Jul 2023Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical... (Clinical Trial)
Clinical Trial
BACKGROUND
Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh.
METHODS
Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6-37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression.
RESULTS
We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2-3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations.
CONCLUSIONS
We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh-higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples counseling.
Topics: Adult; Child, Preschool; Female; Humans; Infant; alpha-Thalassemia; Bangladesh; beta-Thalassemia; Hemoglobinopathies; Prevalence
PubMed: 37468973
DOI: 10.1186/s13023-023-02821-3 -
Gene Oct 2022Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation,...
INTRODUCTION
Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation, developmental abnormalities and/or speech delay and facial dysmorphism, which is termed ATR-16 syndrome. Here, we reported two novel 16p13.3 deletions involving the α-globin gene cluster and multispecies conserved sequences (MCSs), causing only a phenotype of α-thalassemia.
METHODS
Samples were collected from members of the two families and were subjected to haematological and comprehensive genetic analysis.
RESULTS
The novel 108 Kb deletion in family A extends from the non-protein coding RNA gene (WASIR2) to the NPRL3 gene, removing MCS-R1 to R3. This deletion should arise de novo because it wasn't detected in both parents. The novel 336 Kb deletion in family B should extend from telomere to ∼ chr16:336000, removing the entire α-globin gene cluster. Carriers of these two deletions presented with microcytosis and hypochromic red cells, in accordance with a phenotype of α-thalassemia carrier.
CONCLUSION
Our study increases the mutation spectrum of α-thalassemia. MCSs deletion should be considered in clinical practice of thalassemia screening and diagnosis.
Topics: Asian People; China; GTPase-Activating Proteins; Humans; Multigene Family; alpha-Globins; alpha-Thalassemia
PubMed: 35905847
DOI: 10.1016/j.gene.2022.146767 -
Journal of Dentistry For Children... Sep 2021Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome affects males and is associated with profound developmental delay, facial dysmorphism, genital...
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome affects males and is associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Appropriate oral health management for affected patients is important. The purposes of this report are to describe a case involving six years of oral health management, including training in eating, drinking and swallowing, for a patient with ATR-X syndrome, and to discuss the morphological and functional oral characteristics of this disorder. The patient's oral dysfunctions were incompetent lip-closing, inappropriate tongue protrusion, deviation of chewing acquisition, and incompetent oral and pharyngeal bolus propulsion. Other problems included inappropriate ingestion posture, low interest in meals, and poor oral hygiene. A stable oral intake and an improved eating posture were achieved through an intervention; however, the patient's inappropriate tongue protrusion, deviation of chewing acquisition, and incompetent bolus propulsion remained unchanged.
Topics: Child; Humans; Intellectual Disability; Male; Mental Retardation, X-Linked; Oral Health; alpha-Thalassemia
PubMed: 34937632
DOI: No ID Found -
Hemoglobin Mar 2021We describe a new α-globin chain variant in a Chinese subject. This novel variant, with a Val→Met substitution at codon 93 of the α-globin chain, has been named Hb...
We describe a new α-globin chain variant in a Chinese subject. This novel variant, with a Val→Met substitution at codon 93 of the α-globin chain, has been named Hb Qingcheng (: c.280G>A) for where the proband was born. A woman with somatic mosaicism for Hb Qingcheng presented with the phenotype of mild α-thalassemia (α-thal).
Topics: Female; Hemoglobins, Abnormal; Humans; Mutation; Phenotype; alpha-Globins; alpha-Thalassemia
PubMed: 33775194
DOI: 10.1080/03630269.2021.1904975 -
Annals of Human Genetics Mar 2022Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different...
BACKGROUND
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different geographic distributions worldwide. Our aim is to report hematological and molecular findings of G6PD deficient Mexican patients in coinheritance with suggestive hereditary spherocytosis (sHS) and α-thal.
METHODS
We studied 78 G6PD deficiency patients. Hematological parameters, acidified glycerol lysis test, erythrocyte morphology, electrophoresis, and hemoglobin quantification were obtained. G6PD and HBA2/HBA1 variants were identified using ARMS-PCR, Gap-PCR, or Sanger sequencing.
RESULTS
Nine G6PD variants were identified; A , A , and A as the most frequent. G6PD Santiago de Cuba and Kamiube were detected in Mexicans for first time. Hematological analysis revealed additional erythrocyte pathologies in 52 patients, 32 with positive osmotic fragility test and spherocytes in blood smear (suggestive hereditary spherocytosis, sHS), 12 with microcytosis and 8 with all three defects who had the most severe phenotype, with significantly lower hematological parameters (Hb, PCV, MCV, and MCH). α-thal variants (α α, α α and -α ) were observed in 65% of patients with microcytosis.
CONCLUSION
Additional erythrocyte defects were observed in 69.3% of G6PD deficiency patients. We stress the importance of searching for the presence of additional erythrocyte hereditary diseases in patients with G6PD deficiency.
Topics: Glucosephosphate Dehydrogenase Deficiency; Humans; Mexico; Phenotype; Polymerase Chain Reaction; alpha-Thalassemia
PubMed: 34844289
DOI: 10.1111/ahg.12451 -
International Journal of Laboratory... Apr 2023The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main... (Review)
Review
Additional value of red blood cell parameters in predicting uncommon α-thalassemia; experience from 10 years of α-globin gene sequencing and copy number variation analysis.
INTRODUCTION
The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2).
METHODS
In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011-2020 (n = 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014-2020 (n = 6495).
RESULTS
In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples.
CONCLUSION
Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation.
Topics: Child; Adult; Humans; alpha-Thalassemia; DNA Copy Number Variations; alpha-Globins; Erythrocytes; Hemoglobinopathies; Erythrocyte Indices
PubMed: 36567661
DOI: 10.1111/ijlh.14010 -
Scientific Reports Aug 2022α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening...
α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/-- (4.066%), αα/-α (2.934%), αα/-α (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14-99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (-α/-α, αα/--, -α/--, -α/--). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/--, 94.87% for αα/-α, and 96.51% for αα/-α; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
Topics: Cell-Free Nucleic Acids; China; Female; Genotype; Humans; Mutation; Polymerase Chain Reaction; Pregnancy; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35945425
DOI: 10.1038/s41598-022-17718-7