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name: Alpha Thalassemia
creation_date: '2026-02-16T18:18:07Z'
updated_date: '2026-04-22T20:13:21Z'
category: Mendelian
parents:
- Hematological Disease
- Genetic Disease
disease_term:
preferred_term: alpha thalassemia
term:
id: MONDO:0011399
label: alpha thalassemia spectrum
has_subtypes:
- name: Silent Carrier (One Alpha-Globin Gene Deleted)
description: >
Loss of one alpha-globin gene (-α/αα). Clinically silent with normal
hematologic parameters or minimal microcytosis. Detected only by molecular
testing.
- name: Alpha Thalassemia Trait (Two Alpha-Globin Genes Deleted)
description: >
Loss of two alpha-globin genes, either in cis (--/αα) or trans (-α/-α).
Mild microcytic hypochromic anemia. The cis form (common in Southeast
Asian populations) carries risk of hydrops fetalis in offspring.
- name: Hemoglobin H Disease (Three Alpha-Globin Genes Deleted)
description: >
Loss of three alpha-globin genes (--/-α). Moderate hemolytic anemia with
HbH inclusions on brilliant cresyl blue staining. Phenotype ranges from
mild to transfusion-dependent, particularly in non-deletional forms.
- name: Hemoglobin Bart Hydrops Fetalis Syndrome (Four Alpha-Globin Genes Deleted)
description: >
Loss of all four alpha-globin genes (--/--). Severe intrauterine anemia,
hydrops fetalis, and usually death in the neonatal period without
intrauterine intervention.
prevalence:
- population: Global carriers
notes: >
Alpha thalassemia is widespread in tropical and subtropical regions.
More than 100 varieties have been identified. Highest prevalence in
Southeast Asia, southern China, the Mediterranean, Middle East, and Africa.
evidence:
- reference: PMID:25390741
reference_title: "The α-thalassemias."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "More than 100 varieties of α-thalassemia have been identified."
explanation: Confirms the extensive genetic heterogeneity of alpha-thalassemia worldwide.
inheritance:
- name: Autosomal recessive
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Alpha-thalassemia is usually inherited in an autosomal recessive manner"
explanation: GeneReviews confirms autosomal recessive inheritance pattern.
pathophysiology:
- name: Defective Alpha-Globin Synthesis
description: >
Deletions or point mutations in HBA1 and/or HBA2 genes reduce or abolish
alpha-globin chain production. Large deletions are the most common cause,
removing one or both alpha-globin genes on chromosome 16p13.3. Non-deletional
mutations (point mutations, small insertions/deletions) tend to produce more
severe phenotypes for the same number of affected alleles.
genes:
- preferred_term: HBA1
term:
id: hgnc:4823
label: HBA1
- preferred_term: HBA2
term:
id: hgnc:4824
label: HBA2
biological_processes:
- preferred_term: hemoglobin biosynthetic process
modifier: DECREASED
term:
id: GO:0042541
label: hemoglobin biosynthetic process
cell_types:
- preferred_term: erythroblast
term:
id: CL:0000765
label: erythroblast
downstream:
- target: Beta-Globin Chain Excess and Hemoglobin H Formation
description: >
Reduced alpha-globin production leads to excess unpaired beta-globin
chains that form unstable HbH tetramers (beta4).
evidence:
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin"
explanation: Confirms the core defect of reduced alpha-globin chain synthesis causing globin chain imbalance.
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "biallelic pathogenic variants in both HBA1 and HBA2 that result in deletion or inactivation of all four"
explanation: Confirms that pathogenic variants in HBA1 and HBA2 cause alpha-thalassemia through gene deletion or inactivation.
- name: Beta-Globin Chain Excess and Hemoglobin H Formation
description: >
In the absence of sufficient alpha-globin chains, excess beta-globin chains
form unstable tetramers called hemoglobin H (beta4). HbH precipitates as
inclusion bodies in mature red cells, causing membrane damage and premature
destruction. In the most severe form (Hb Bart syndrome), excess gamma-globin
chains form hemoglobin Bart (gamma4), which has extremely high oxygen
affinity and cannot deliver oxygen to tissues.
biological_processes:
- preferred_term: response to oxidative stress
modifier: INCREASED
term:
id: GO:0006979
label: response to oxidative stress
- preferred_term: hemoglobin biosynthetic process
modifier: ABNORMAL
term:
id: GO:0042541
label: hemoglobin biosynthetic process
cell_types:
- preferred_term: erythrocyte
term:
id: CL:0000232
label: erythrocyte
downstream:
- target: Chronic Hemolytic Anemia
description: >
HbH inclusion bodies cause oxidative membrane damage and shortened
red cell survival.
evidence:
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities"
explanation: Confirms that alpha-thalassemia leads to ineffective erythropoiesis, decreased RBC survival, and chronic hemolytic anemia.
- name: Chronic Hemolytic Anemia
description: >
Peripheral destruction of red blood cells containing HbH inclusions.
In HbH disease, hemolysis is typically chronic and compensated but may
become acutely exacerbated by infections, oxidant drugs, or pregnancy.
In Hb Bart syndrome, the anemia is severe and incompatible with
extrauterine life without intervention.
biological_processes:
- preferred_term: erythrocyte homeostasis
modifier: ABNORMAL
term:
id: GO:0034101
label: erythrocyte homeostasis
cell_types:
- preferred_term: erythrocyte
term:
id: CL:0000232
label: erythrocyte
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
downstream:
- target: Iron Overload
description: Iron released from hemolyzed red cells contributes to iron loading.
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "may develop gallstones and experience acute episodes of hemolysis in response to infections or exposure to oxidant drugs"
explanation: Confirms episodic hemolysis triggered by infections or oxidant drugs in HbH disease.
- name: Ineffective Erythropoiesis
description: >
Expanded but ineffective erythroid compartment in bone marrow. Erythroid
precursors are damaged by precipitated globin chains, leading to intramedullary
apoptosis. More prominent in non-deletional HbH disease and Hb Bart syndrome.
biological_processes:
- preferred_term: erythrocyte differentiation
modifier: ABNORMAL
term:
id: GO:0030218
label: erythrocyte differentiation
- preferred_term: apoptotic process
modifier: INCREASED
term:
id: GO:0006915
label: apoptotic process
cell_types:
- preferred_term: erythroid progenitor cell
term:
id: CL:0000038
label: erythroid progenitor cell
downstream:
- target: Iron Overload
description: >
Ineffective erythropoiesis suppresses hepcidin, increasing
intestinal iron absorption.
evidence:
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia"
explanation: Confirms ineffective erythropoiesis as a key therapeutic target in alpha-thalassemia.
- name: Iron Overload
description: >
Iron accumulation from chronic transfusions and increased intestinal
absorption (due to hepcidin suppression from ineffective erythropoiesis
and hemolysis). Particularly significant in transfusion-dependent
non-deletional HbH disease and surviving Hb Bart patients.
biological_processes:
- preferred_term: intracellular iron ion homeostasis
modifier: ABNORMAL
term:
id: GO:0006879
label: intracellular iron ion homeostasis
- preferred_term: iron ion transport
modifier: INCREASED
term:
id: GO:0006826
label: iron ion transport
cell_types:
- preferred_term: hepatocyte
term:
id: CL:0000182
label: hepatocyte
evidence:
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "chelation therapy for iron overload"
explanation: Confirms iron overload as a recognized complication requiring chelation therapy.
phenotypes:
- category: Hematological
name: Hypochromic Microcytic Anemia
description: >
Reduced hemoglobin synthesis leads to small, pale red blood cells.
Severity ranges from absent (silent carriers) to profound (Hb Bart
syndrome). HbH disease typically shows moderate anemia with Hb 7-10 g/dL.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: hypochromic microcytic anemia
term:
id: HP:0004840
label: Hypochromic microcytic anemia
evidence:
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease"
explanation: Confirms the wide spectrum of anemia severity across alpha-thalassemia genotypes.
- category: Hematological
name: Decreased Mean Corpuscular Volume
description: >
Low MCV is the hallmark laboratory finding in alpha-thalassemia trait
and HbH disease. Often the initial finding prompting further evaluation.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: decreased mean corpuscular volume
term:
id: HP:0025066
label: Decreased mean corpuscular volume
- category: Hematological
name: Hemolytic Anemia
description: >
Chronic hemolysis from HbH inclusion body-mediated membrane damage.
Acute exacerbations triggered by infections or oxidant drugs.
frequency: FREQUENT
phenotype_term:
preferred_term: hemolytic anemia
term:
id: HP:0001878
label: Hemolytic anemia
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "experience acute episodes of hemolysis in response to infections or exposure to oxidant drugs"
explanation: Confirms episodic hemolytic anemia triggered by infections or oxidant drugs.
- category: Hematological
name: Reticulocytosis
description: >
Elevated reticulocyte count reflecting compensatory erythropoietic
drive in response to chronic hemolysis.
frequency: FREQUENT
phenotype_term:
preferred_term: reticulocytosis
term:
id: HP:0001923
label: Reticulocytosis
- category: Hematological
name: Extramedullary Hematopoiesis
description: >
Compensatory hematopoiesis in liver, spleen, and other sites.
Marked in Hb Bart syndrome and severe HbH disease.
frequency: FREQUENT
phenotype_term:
preferred_term: extramedullary hematopoiesis
term:
id: HP:0001978
label: Extramedullary hematopoiesis
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Extramedullary erythropoiesis, marked hepatosplenomegaly, and a massive placenta are common"
explanation: Confirms extramedullary hematopoiesis as a common feature of severe alpha-thalassemia.
- category: Prenatal
name: Hydrops Fetalis
description: >
Generalized edema with pleural and pericardial effusions due to
severe fetal anemia in Hb Bart syndrome (--/--). The hallmark of
the most severe form of alpha-thalassemia.
frequency: VERY_FREQUENT
notes: Specific to Hb Bart syndrome (four-gene deletion)
phenotype_term:
preferred_term: hydrops fetalis
term:
id: HP:0001789
label: Hydrops fetalis
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "characterized by prenatal onset of generalized edema and pleural and pericardial effusions as a result of congestive heart failure induced by severe anemia"
explanation: Confirms hydrops fetalis as the defining feature of Hb Bart syndrome, caused by severe fetal anemia.
- category: Gastrointestinal
name: Splenomegaly
description: >
Splenic enlargement from extramedullary hematopoiesis and increased
erythrocyte destruction. Present in most individuals with HbH disease.
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: splenomegaly
term:
id: HP:0001744
label: Splenomegaly
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The majority of individuals have enlargement of the spleen (and less commonly of the liver), mild jaundice, and sometimes thalassemia-like bone changes"
explanation: Confirms splenomegaly as a majority finding in HbH disease.
- category: Gastrointestinal
name: Hepatomegaly
description: >
Liver enlargement from extramedullary hematopoiesis and iron
deposition. Less common than splenomegaly.
frequency: FREQUENT
phenotype_term:
preferred_term: hepatomegaly
term:
id: HP:0002240
label: Hepatomegaly
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "enlargement of the spleen (and less commonly of the liver)"
explanation: Confirms hepatomegaly is present but less common than splenomegaly.
- category: Gastrointestinal
name: Cholelithiasis
description: >
Pigment gallstones from chronic bilirubin overproduction
secondary to hemolysis.
frequency: FREQUENT
phenotype_term:
preferred_term: cholelithiasis
term:
id: HP:0001081
label: Cholelithiasis
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "may develop gallstones and experience acute episodes of hemolysis"
explanation: Confirms gallstone formation in individuals with HbH disease.
- category: Metabolic
name: Jaundice
description: >
Unconjugated hyperbilirubinemia from chronic hemolysis.
Typically mild in HbH disease.
frequency: FREQUENT
phenotype_term:
preferred_term: jaundice
term:
id: HP:0000952
label: Jaundice
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "mild jaundice, and sometimes thalassemia-like bone changes"
explanation: Confirms mild jaundice as a feature of HbH disease.
- category: Metabolic
name: Iron Overload
description: >
Increased serum ferritin and tissue iron deposition, particularly in
transfusion-dependent patients or those with non-deletional HbH disease.
frequency: FREQUENT
phenotype_term:
preferred_term: increased circulating ferritin concentration
term:
id: HP:0003281
label: Increased circulating ferritin concentration
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "iron chelation therapy should be instituted"
explanation: Confirms that iron overload requiring chelation occurs in chronically transfused HbH disease patients.
- category: Cardiovascular
name: Congestive Heart Failure
description: >
Severe anemia-induced heart failure in Hb Bart syndrome.
May also occur in severe non-deletional HbH disease or
with chronic iron overload.
frequency: VERY_FREQUENT
notes: Specific to Hb Bart syndrome; occasional in severe HbH disease
phenotype_term:
preferred_term: congestive heart failure
term:
id: HP:0001635
label: Congestive heart failure
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "congestive heart failure induced by severe anemia"
explanation: Confirms congestive heart failure as a consequence of severe anemia in Hb Bart syndrome.
- category: Skeletal
name: Thalassemia-like Bone Changes
description: >
Skeletal changes from marrow expansion, including frontal bossing
and maxillary overgrowth. Seen in more severe forms of HbH disease.
frequency: OCCASIONAL
phenotype_term:
preferred_term: frontal bossing
term:
id: HP:0002007
label: Frontal bossing
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "sometimes thalassemia-like bone changes"
explanation: Confirms thalassemia-like bone changes can occur in HbH disease.
biochemical:
- name: Hemoglobin H
presence: Present
context: HbH (beta4 tetramers) detected in HbH disease; 5-40% of total hemoglobin
- name: Hemoglobin Bart
presence: Present
context: Hb Bart (gamma4 tetramers) predominates in Hb Bart hydrops fetalis syndrome
- name: Hemoglobin
presence: Decreased
context: Hb 7-10 g/dL in typical HbH disease; severely reduced in Hb Bart syndrome
- name: MCV
presence: Decreased
context: Low MCV in trait and HbH disease; key screening parameter
- name: Serum Ferritin
presence: Variable
context: May be elevated in non-deletional HbH disease and transfusion-dependent patients
genetic:
- name: HBA1
association: Causative
inheritance:
- name: Autosomal recessive
notes: >
Alpha-globin gene on chromosome 16p13.3. Deletions removing one or both
copies are the most common cause of alpha-thalassemia. Non-deletional
mutations (e.g., Hb Constant Spring, Hb Quong Sze) produce more severe
phenotypes for the same number of affected alleles.
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "biallelic pathogenic variants in both HBA1 and HBA2 that result in deletion or inactivation of all four"
explanation: Confirms HBA1 and HBA2 pathogenic variants cause alpha-thalassemia.
- name: HBA2
association: Causative
inheritance:
- name: Autosomal recessive
notes: >
Alpha-globin gene on chromosome 16p13.3, tandemly duplicated with HBA1.
The two genes produce identical alpha-globin protein. HBA2 contributes
slightly more to total alpha-globin output than HBA1.
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "biallelic pathogenic variants in HBA1 and HBA2 that result in deletion or inactivation of three"
explanation: Confirms HBA2 involvement in alpha-thalassemia pathogenesis.
treatments:
- name: Red Blood Cell Transfusions
description: >
Occasional transfusions for hemolytic or aplastic crises in HbH disease.
Regular transfusions may be needed for non-deletional HbH disease.
Intrauterine transfusions can be life-saving for Hb Bart syndrome.
notes: >
Applies to Hemoglobin H Disease during hemolytic/aplastic crises or severe
transfusion-dependent disease, and to Hemoglobin Bart Hydrops Fetalis
Syndrome as intrauterine or postnatal transfusion support. Not indicated for
silent carrier state or alpha-thalassemia trait.
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "occasional red blood cell transfusions may be needed during hemolytic or aplastic crises"
explanation: Confirms occasional transfusion needs during crises in HbH disease.
- name: Iron Chelation Therapy
description: >
For patients who require chronic transfusions or have non-transfusional
iron loading. Deferasirox can reduce liver iron concentration in
non-transfusion-dependent patients.
notes: >
Applies to Hemoglobin H Disease with chronic transfusion exposure or
non-transfusional iron loading, and to surviving Hemoglobin Bart syndrome
patients if transfusion-related iron overload develops. Not indicated for
silent carrier state or uncomplicated alpha-thalassemia trait.
treatment_term:
preferred_term: iron chelation therapy
term:
id: MAXO:0001223
label: chelator agent therapy
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "iron chelation with deferasirox can be considered to reduce liver iron concentration"
explanation: Confirms deferasirox-based iron chelation for non-transfusion-dependent patients.
- reference: PMID:38182489
reference_title: "Αlpha-thalassemia: A practical overview."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "chelation therapy for iron overload"
explanation: Confirms chelation therapy as part of alpha-thalassemia management.
- name: Splenectomy
description: >
Considered when hypersplenism increases transfusion requirements or
worsens anemia. Carries risk of post-splenectomy infections and
thrombosis.
notes: >
Applies primarily to selected Hemoglobin H Disease patients with
symptomatic hypersplenism or escalating transfusion needs. Not indicated for
silent carrier state, alpha-thalassemia trait, or routine Hb Bart syndrome
care.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Hematopoietic Stem Cell Transplantation
description: >
Potentially curative for surviving Hb Bart syndrome patients and
severe transfusion-dependent HbH disease. Rarely performed.
notes: >
Applies to severe transfusion-dependent Hemoglobin H Disease and selected
surviving Hemoglobin Bart syndrome patients. Not indicated for silent
carrier state or alpha-thalassemia trait.
treatment_term:
preferred_term: hematopoietic stem cell transplantation
term:
id: MAXO:0000747
label: hematopoietic stem cell transplantation
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "rarely curative hematopoietic stem cell transplant may allow survival of children"
explanation: Confirms HSCT as a rare but curative option for severe alpha-thalassemia.
- name: Avoidance of Oxidant Drugs
description: >
Patients with HbH disease should avoid oxidant drugs that can trigger
acute hemolytic crises (same drugs as avoided in G6PD deficiency).
notes: >
Applies to Hemoglobin H Disease and, as a precaution, alpha-thalassemia
trait. Same agents as those avoided in G6PD deficiency.
- name: Genetic Counseling
description: >
Carrier screening and genetic counseling for at-risk populations,
especially those of Southeast Asian, Chinese, and Mediterranean descent
where cis deletions (--/αα) are common.
notes: >
Applies to all subtypes and carriers. Cis two-gene deletions (--/αα) need
explicit reproductive-risk interpretation because two cis-carrier parents
have risk for Hb Bart syndrome offspring.
treatment_term:
preferred_term: genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Couples who are members of populations at risk"
explanation: Confirms the importance of carrier testing in at-risk populations.
- name: Mitapivat (AQVESME)
description: >
Oral pyruvate kinase activator pharmacotherapy for anemia in adults with
transfusion-dependent or non-transfusion-dependent alpha- or
beta-thalassemia.
notes: >
Applies to adult patients with clinically significant alpha-thalassemia,
especially Hemoglobin H Disease with transfusion-dependent or
non-transfusion-dependent anemia. Not studied for silent carrier state or
uncomplicated alpha-thalassemia trait; experience in surviving Hb Bart
syndrome patients remains limited.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: Mitapivat
term:
id: NCIT:C157039
label: Mitapivat
evidence:
- reference: url:https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-treatment-anemia-thalassemia-inherited-blood-disorder
reference_title: "FDA approves first oral treatment for anemia in thalassemia, an inherited blood disorder | FDA"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "approved Aqvesme (mitapivat) tablets to treat anemia"
explanation: >
FDA approval notice supports Aqvesme/mitapivat as an approved anemia
treatment for thalassemia.
- reference: clinicaltrials:NCT04770753
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The primary purpose of this study was to compare the effect of mitapivat versus placebo on hemolytic anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT)."
explanation: >
ENERGIZE supports clinical evaluation of mitapivat for non-transfusion-
dependent alpha- or beta-thalassemia anemia.
- reference: clinicaltrials:NCT04770779
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The primary objective of this study was to compare the effect of mitapivat versus placebo on transfusion burden in participants with α- or β-transfusion-dependent thalassemia."
explanation: >
ENERGIZE-T supports clinical evaluation of mitapivat for transfusion-
dependent alpha- or beta-thalassemia.
diagnosis:
- name: Complete Blood Count and Red-Cell Indices
description: >
Initial hematologic evaluation uses complete blood count and red-cell
indices to detect microcytosis, hypochromia, and anemia severity, and helps
stratify silent carrier, alpha-thalassemia trait, HbH disease, and Hb Bart
syndrome before molecular confirmation.
diagnosis_term:
preferred_term: complete blood count
term:
id: MAXO:0001509
label: blood cell count
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "hematologic and hemoglobin (Hb) findings"
explanation: >
GeneReviews states that characteristic hematologic and hemoglobin findings
are part of establishing alpha-thalassemia diagnoses.
- name: Hemoglobin Electrophoresis and HbH Inclusion Assessment
description: >
Hemoglobin analysis by electrophoresis, HPLC, or comparable fractionation
detects HbH or Hb Bart patterns, while supravital staining for HbH inclusion
bodies supports HbH disease classification.
diagnosis_term:
preferred_term: hemoglobin electrophoresis test
term:
id: MAXO:0000855
label: hemoglobin electrophoresis test
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "hematologic and Hb findings and molecular genetic testing"
explanation: >
GeneReviews supports hemoglobin findings alongside molecular testing for
establishing HbH disease diagnosis.
- name: Molecular Genetic Testing for HBA1/HBA2
description: >
Deletion/duplication testing and sequence analysis of HBA1 and HBA2 identify
one-, two-, three-, or four-alpha-globin allele loss/inactivation, including
common deletional alleles and non-deletional variants such as Hb Constant
Spring. Cis/trans interpretation distinguishes --/αα carrier risk from
-α/-α trans trait and guides recurrence counseling.
diagnosis_term:
preferred_term: molecular genetic testing
term:
id: MAXO:0000533
label: molecular genetic testing
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "molecular genetic testing that identifies biallelic pathogenic variants in HBA1 and HBA2"
explanation: >
GeneReviews identifies molecular testing of HBA1 and HBA2 as diagnostic
confirmation for clinically significant alpha-thalassemia.
- name: Prenatal Genetic Testing for Hb Bart Syndrome Risk
description: >
Prenatal or preimplantation genetic testing is used when parental genotypes
create high risk for Hb Bart syndrome, especially when both parents carry a
two-gene deletion in cis (--/αα) or when one cis carrier has an unavailable
or unknown partner genotype.
diagnosis_term:
preferred_term: prenatal genetic testing
term:
id: MAXO:0000529
label: prenatal genetic testing
evidence:
- reference: PMID:20301608
reference_title: "Alpha-Thalassemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Prenatal and preimplantation genetic testing may be carried out for couples who are at high risk of having a fetus with Hb Bart syndrome"
explanation: >
GeneReviews supports prenatal and preimplantation genetic testing for
couples at high risk for Hb Bart syndrome.
clinical_trials:
- name: NCT04770753
phase: PHASE_III
status: ACTIVE_NOT_RECRUITING
description: >
ENERGIZE randomized placebo-controlled trial of mitapivat in adults with
non-transfusion-dependent alpha- or beta-thalassemia.
target_phenotypes:
- preferred_term: Hemolytic anemia
term:
id: HP:0001878
label: Hemolytic anemia
evidence:
- reference: clinicaltrials:NCT04770753
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The primary purpose of this study was to compare the effect of mitapivat versus placebo on hemolytic anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT)."
explanation: >
ClinicalTrials.gov summary identifies the ENERGIZE trial and its
hemolytic-anemia endpoint in non-transfusion-dependent thalassemia.
- name: NCT04770779
phase: PHASE_III
status: ACTIVE_NOT_RECRUITING
description: >
ENERGIZE-T randomized placebo-controlled trial of mitapivat in adults with
transfusion-dependent alpha- or beta-thalassemia.
target_phenotypes:
- preferred_term: Hypochromic microcytic anemia
term:
id: HP:0004840
label: Hypochromic microcytic anemia
evidence:
- reference: clinicaltrials:NCT04770779
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The primary objective of this study was to compare the effect of mitapivat versus placebo on transfusion burden in participants with α- or β-transfusion-dependent thalassemia."
explanation: >
ClinicalTrials.gov summary identifies the ENERGIZE-T trial and its
transfusion-burden endpoint in transfusion-dependent thalassemia.
datasets:
references:
- reference: PMID:20301608
title: "Alpha-Thalassemia."
tags:
- GeneReviews
findings: []
- reference: DOI:10.1177/1753495x231207676
title: 'Thalassemia screening by third-generation sequencing: Pilot study in a Thai population'
findings: []
- reference: clinicaltrials:NCT04770753
title: 'A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE)'
findings: []
- reference: clinicaltrials:NCT04770779
title: 'A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE-T)'
findings: []
- reference: url:https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-treatment-anemia-thalassemia-inherited-blood-disorder
title: "FDA approves first oral treatment for anemia in thalassemia, an inherited blood disorder | FDA"
findings: []
- reference: DOI:10.1182/hematology.2023000468
title: 'Pyruvate kinase activators: targeting red cell metabolism in thalassemia'
findings: []
- reference: DOI:10.1186/s12884-023-06232-x
title: 'Fetal hemodynamic changes and mitochondrial dysfunction in myocardium and brain tissues in response to anemia: a lesson from hemoglobin Bart’s disease'
findings: []
- reference: DOI:10.1371/journal.pone.0306043
title: METTL16 participates in haemoglobin H disease through m6A modification
findings: []
- reference: DOI:10.18535/cmhrj.v4i2.325
title: 'Prevalence of Thalassemia in Nigeria: Pathophysiology and Clinical Manifestations'
findings: []
- reference: DOI:10.3389/fgene.2024.1356068
title: Screening for thalassemia carriers among the Han population of childbearing age in Southwestern of China
findings: []
- reference: DOI:10.3389/fgene.2024.1422462
title: A particular focus on the prevalence of α-thalassemia and β-thalassemia among pregnant women in Changsha County, Hunan Province
findings: []
- reference: DOI:10.3389/fmed.2022.1015306
title: Comparisons of serum non-transferrin-bound iron levels and fetal cardiac function between fetuses affected with hemoglobin Bart’s disease and normal fetuses
findings: []
- reference: DOI:10.3389/fped.2024.1467760
title: 'Hotspots and status of Fetal Alpha-Thalassemia from 2009 to 2023: a bibliometric analysis'
findings: []
- reference: DOI:10.3390/ijms24065658
title: Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease
findings: []
- reference: DOI:10.3390/ijms25063400
title: 'Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management'
findings: []
- reference: DOI:10.3390/ijms252011246
title: Erythropoiesis and Gene Expression Analysis in Erythroid Progenitor Cells Derived from Patients with Hemoglobin H/Constant Spring Disease
findings: []
- reference: DOI:10.3390/thalassrep14040010
title: 'Thalassemia: Pathophysiology, Diagnosis, and Advances in Treatment'
findings: []
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on the pathophysiology of Alpha Thalassemia. Focus on the molecular and cellular mechanisms underlying disease progression.
Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs
Alpha thalassemia is a quantitative hemoglobinopathy caused by reduced production of α-globin chains due to pathogenic variants affecting the α-globin gene cluster, most commonly deletions involving HBA1/HBA2 on chromosome 16. Severity follows α-globin gene dosage: silent carrier (1 allele affected), α-thalassemia trait (2), HbH disease (3), and Hb Bart’s hydrops fetalis / α-thalassemia major (4). (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, zahed2023effectiveutilizationof pages 64-67)
A central mechanistic concept is globin-chain imbalance: α-globin deficiency leaves excess non-α chains that self-associate into homotetramers—HbH (β4) postnatally and Hb Bart’s (γ4) in fetal life—both of which are poor oxygen carriers and/or unstable, driving downstream RBC injury. (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, zahed2023effectiveutilizationof pages 64-67)
Loss or dysfunction of HBA1/HBA2 reduces α-globin synthesis; clinical severity is determined by the number of affected α-globin genes. (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, sadiq2024thalassemiapathophysiologydiagnosis pages 6-7)
In HbH disease (three α genes affected), excess β chains form β4 tetramers (HbH); HbH is described as unstable, prone to oxidative damage and precipitation in erythroid cells, shortening RBC lifespan and increasing hemolysis. (zahed2023effectiveutilizationof pages 64-67)
In fetal Hb Bart’s disease (four α genes affected), fetuses produce only Hb Bart’s (γ4); Hb Bart’s has high oxygen affinity and is associated with widespread fetal tissue hypoxia and severe anemia, leading to hydrops fetalis and multi-organ injury. (chaemsaithong2023placentaderivedextracellularvesicles pages 1-2, luewan2024fetalhemodynamicchanges pages 4-6)
A unifying downstream mechanism in thalassemia is oxidative stress from precipitated/excess globin and iron, which drives both hemolysis and ineffective erythropoiesis. (kuo2023pyruvatekinaseactivators pages 1-2)
In an authoritative hematology education review, oxidative stress is described as a “major factor” that drives hemolysis and ineffective erythropoiesis in thalassemia, and the oxidative burden can reduce pyruvate kinase activity and ATP availability, worsening red cell integrity and survival. (kuo2023pyruvatekinaseactivators pages 1-2)
In alpha thalassemia, globin imbalance injures erythroid precursors, contributing to ineffective erythropoiesis and intramedullary destruction/hemolysis, manifesting as microcytic hypochromic anemia. (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, sadiq2024thalassemiapathophysiologydiagnosis pages 6-7)
Patient-derived erythroid progenitors from HbH/Constant Spring (HbH/CS) demonstrate cellular correlates of IE: a trend toward increased proliferation, reduced viability, and delayed terminal differentiation, consistent with maturation inefficiency under α/β imbalance. (wongkhammul2024erythropoiesisandgene pages 2-4, wongkhammul2024erythropoiesisandgene pages 1-2)
A 2024 prospective study of 18 Hb Bart’s fetuses vs 13 controls (~19 weeks gestation) showed severe fetal anemia (Hb 6.4±1.3 vs 11.2±1.2 g/dL, p<0.001) with hemodynamic compensation (increased cardiac dimensions and combined cardiac output) but evidence of mitochondrial structural and functional injury in heart/brain (mitochondrial swelling/unfolded cristae; increased membrane potential changes; increased ROS particularly in brain). (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2)
A complementary 2023 prospective cordocentesis study (20 affected vs 30 controls) found increased fetal serum iron and non-transferrin-bound iron (NTBI/LPI) in Hb Bart’s fetuses (NTBI median 0.11 vs 0.07, p=0.046), and NTBI correlated with worse myocardial performance indices, linking anemia/iron dysregulation to fetal cardiac dysfunction in the pre-hydropic stage. (jatavan2023comparisonsofserum pages 1-2, jatavan2023comparisonsofserum pages 4-5)
Hb Constant Spring is caused by HBA2:c.427T>C, which replaces the termination codon and produces an elongated α-globin chain (+31 aa) that can form abnormal precipitates and alter RBC membrane proteins; compound heterozygosity with α0-thalassemia can produce more severe HbH/CS disease. (wongkhammul2024erythropoiesisandgene pages 1-2)
Epitranscriptomic (m6A) modifiers in HbH disease: A 2024 PLOS ONE study implicated METTL16 (m6A writer) and readers including YTHDF3 and IGF2BP3 in HbH phenotypic heterogeneity, reporting METTL16 downregulation (FC 0.44, P<0.001) and correlations with IGF2BP3 (R=0.81, P=0.004) and YTHDF3 (R=0.74, P=0.01). IGF2BP3 expression was negatively correlated with hemoglobin in patients (P<0.001). Functional perturbation in K562 cells linked METTL16 to ROS and intracellular iron changes and altered hemin-induced hemoglobin synthesis. (liao2024mettl16participatesin pages 7-8, liao2024mettl16participatesin pages 1-2)
Proteostasis/chaperone response: HbH/CS erythroid progenitors showed elevated expression of molecular chaperones (HSP and CCT gene families), consistent with proteotoxic stress from unstable globin products. (wongkhammul2024erythropoiesisandgene pages 1-2)
Key dysregulated processes include: - Hemoglobin assembly and oxygen transport disrupted by abnormal tetramers (HbH, Hb Bart’s). (zahed2023effectiveutilizationof pages 64-67, chaemsaithong2023placentaderivedextracellularvesicles pages 1-2) - Oxidative stress / ROS homeostasis driven by unstable hemoglobin species and iron dysregulation; linked to membrane damage and erythroid cell death. (kuo2023pyruvatekinaseactivators pages 1-2, jatavan2023comparisonsofserum pages 4-5) - Erythroid differentiation and maturation delays/arrest and reduced erythroblast viability (ineffective erythropoiesis). (wongkhammul2024erythropoiesisandgene pages 2-4, sadiq2024thalassemiapathophysiologydiagnosis pages 4-6) - Iron handling abnormalities in severe fetal disease (increased NTBI/LPI) and downstream tissue injury risk. (jatavan2023comparisonsofserum pages 1-2, jatavan2023comparisonsofserum pages 4-5) - Mitochondrial dysfunction in fetal target organs under hypoxic anemia (mitochondrial swelling/cristae changes; increased ΔΨm changes and ROS). (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2)
(Selected GO-like terms; intended for knowledge-base mapping) - Hemoglobin biosynthetic process / hemoglobin metabolic process (α-globin deficiency; abnormal HbH/Hb Bart’s production). (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, zahed2023effectiveutilizationof pages 64-67) - Erythrocyte differentiation / erythrocyte maturation / erythropoiesis (delayed terminal differentiation; ineffective erythropoiesis). (wongkhammul2024erythropoiesisandgene pages 2-4, sadiq2024thalassemiapathophysiologydiagnosis pages 4-6) - Response to oxidative stress / regulation of reactive oxygen species metabolic process (globin precipitation + iron; fetal tissue ROS increases). (kuo2023pyruvatekinaseactivators pages 1-2, luewan2024fetalhemodynamicchanges pages 4-6) - Response to hypoxia (Hb Bart’s fetal hypoxic anemia driving compensatory hemodynamics and organ injury). (luewan2024fetalhemodynamicchanges pages 4-6, chaemsaithong2023placentaderivedextracellularvesicles pages 1-2) - Iron ion homeostasis / iron ion transport (elevated NTBI/LPI in fetal Hb Bart’s). (jatavan2023comparisonsofserum pages 1-2, jatavan2023comparisonsofserum pages 4-5) - Mitochondrial membrane potential / mitochondrial inner membrane organization (ΔΨm changes; cristae abnormalities in fetal heart/brain). (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2)
1) Genetic lesion (deletions, regulatory deletions, or non-deletional variants) reduces α-globin expression (HBA1/HBA2; enhancer dysfunction such as HS-40/MCS-R2). (isaiah2024prevalenceofthalassemia pages 3-4, traegersynodinos2024impactofαglobin pages 4-5) 2) Globin-chain imbalance produces HbH (β4) postnatally and/or Hb Bart’s (γ4) prenatally (depending on developmental stage and gene dosage). (sadiq2024thalassemiapathophysiologydiagnosis pages 4-6, zahed2023effectiveutilizationof pages 64-67)
3) Unstable hemoglobin species / precipitates → oxidative injury to erythroid precursors and mature RBCs → ineffective erythropoiesis + hemolysis → anemia and compensatory erythropoiesis. (zahed2023effectiveutilizationof pages 64-67, sadiq2024thalassemiapathophysiologydiagnosis pages 4-6) 4) In HbH/CS: erythroid progenitors show delayed differentiation and reduced viability; gene expression reflects reduced HBA1/HBA2 and low α/β ratios. (wongkhammul2024erythropoiesisandgene pages 2-4)
5) Severe fetal anemia drives cardiomegaly and increased cardiac output (compensatory) but leaves residual mitochondrial dysfunction/ROS injury in heart and brain, suggesting “cellular damage secondary to anemic hypoxia” despite compensation. (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2) 6) Elevated fetal NTBI/LPI may contribute additional oxidative stress and correlates with fetal cardiac dysfunction. (jatavan2023comparisonsofserum pages 1-2, jatavan2023comparisonsofserum pages 4-5)
(Representative phenotype groupings; exact HP IDs not enumerated in provided sources) - Microcytic hypochromic anemia in trait and HbH/CS cohorts (low Hb, low MCV/MCH) (wongkhammul2024erythropoiesisandgene pages 2-4, sadiq2024thalassemiapathophysiologydiagnosis pages 4-6) - Chronic hemolytic anemia in HbH disease, often with splenomegaly and hemolysis features (zahed2023effectiveutilizationof pages 64-67) - Hydrops fetalis / fetal cardiomegaly / fetal cardiac dysfunction in Hb Bart’s disease (chaemsaithong2023placentaderivedextracellularvesicles pages 1-2, luewan2024fetalhemodynamicchanges pages 4-6) - Neurologic and cardiac cellular injury risk in utero suggested by fetal brain and myocardial mitochondrial dysfunction and ROS increases (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2)
NGS in reproductive/population screening: - Southwest China Han cohort (Frontiers in Genetics, Apr 2024): 1,093 individuals screened; carrier detection rate 11.89%, with α-thalassemia carriers 7.68% (84/1,093); NGS found an additional 0.91% (10/1,093) rare variants not detected by traditional PCR methods. (du2024screeningforthalassemia pages 1-2) - Changsha County prenatal cohort (Frontiers in Genetics, Nov 2024): 38,810 pregnant women; 5.69% carriers detected by NGS; 1,594 α-thalassemia carriers with 23 genotypes identified. (xia2024aparticularfocus pages 1-2)
Third-generation sequencing (TGS) for hard-to-resolve variants: A Thai pilot study (Obstetric Medicine, Oct 2024) applied TGS to 19 cases; conventional testing left 47.7% undiagnosed, and TGS provided additional diagnoses in 36.8% (7/19). (traisrisilp2024thalassemiascreeningby pages 1-2)
A 2023 review of placenta-derived EVs and Hb Bart’s disease reports: “Sonographic markers can accurately predict fetal Hb Bart’s disease as early as the late first trimester (12–15 weeks of gestation), with a detection rate of 90–95 percent,” and serial ultrasound surveillance can achieve “a sensitivity of 100 percent…with a false positive rate of 10.9 percent” while reducing invasive procedures “by 70 percent.” (chaemsaithong2023placentaderivedextracellularvesicles pages 4-5)
Pyruvate kinase activation (mitapivat): A 2023 American Society of Hematology Education Program review describes oxidative stress as central in thalassemia and positions PK activation as a metabolic therapy. In a phase 2 open-label NTDT study including α-thalassemia (HbH), the primary endpoint (≥1 g/dL Hb increase) was met in 80% (16/20) overall, and all 5 α-thalassemia (HbH) patients met the endpoint. Ongoing phase 3 trials include ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779) in α- or β-thalassemia. (kuo2023pyruvatekinaseactivators pages 3-4, kuo2023pyruvatekinaseactivators pages 4-6)
Recent authoritative reviews emphasize that thalassemia phenotypes arise from a core biochemical lesion (globin imbalance) that triggers oxidative stress, hemolysis, and ineffective erythropoiesis, while newer work adds layers of heterogeneity from modifiers (e.g., RNA methylation machinery). (kuo2023pyruvatekinaseactivators pages 1-2, liao2024mettl16participatesin pages 7-8)
Fetal Hb Bart’s disease demonstrates a clinically important dissociation: measurable hemodynamic compensation can coexist with cellular organ injury (mitochondrial dysfunction and ROS), suggesting that “compensation” does not equal “no damage,” and providing a mechanistic rationale for early detection strategies and (future) in utero interventions. (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2)
The provided full-text evidence extracts include DOIs and journal metadata but do not include PMIDs in the excerpts available to this tool run. Key evidence items with publication dates and URLs include: - Chaemsaithong et al., Int J Mol Sci (Mar 2023): https://doi.org/10.3390/ijms24065658 (chaemsaithong2023placentaderivedextracellularvesicles pages 1-2, chaemsaithong2023placentaderivedextracellularvesicles pages 4-5) - Jatavan et al., Frontiers in Medicine (Jan 2023): https://doi.org/10.3389/fmed.2022.1015306 (jatavan2023comparisonsofserum pages 1-2, jatavan2023comparisonsofserum pages 4-5) - Kuo, ASH Education Program (Dec 2023): https://doi.org/10.1182/hematology.2023000468 (kuo2023pyruvatekinaseactivators pages 3-4, kuo2023pyruvatekinaseactivators pages 4-6) - Luewan et al., BMC Pregnancy and Childbirth (Feb 2024): https://doi.org/10.1186/s12884-023-06232-x (luewan2024fetalhemodynamicchanges pages 4-6, luewan2024fetalhemodynamicchanges pages 1-2) - Du et al., Frontiers in Genetics (Apr 2024): https://doi.org/10.3389/fgene.2024.1356068 (du2024screeningforthalassemia pages 1-2) - Traeger-Synodinos et al., Int J Mol Sci (Mar 2024): https://doi.org/10.3390/ijms25063400 (traegersynodinos2024impactofαglobin pages 4-5) - Liao et al., PLOS ONE (Aug 2024): https://doi.org/10.1371/journal.pone.0306043 (liao2024mettl16participatesin pages 7-8) - Wongkhammul et al., Int J Mol Sci (Oct 2024): https://doi.org/10.3390/ijms252011246 (wongkhammul2024erythropoiesisandgene pages 2-4) - Xia et al., Frontiers in Genetics (Nov 2024): https://doi.org/10.3389/fgene.2024.1422462 (xia2024aparticularfocus pages 1-2) - Traisrisilp et al., Obstetric Medicine (Oct 2024): https://doi.org/10.1177/1753495x231207676 (traisrisilp2024thalassemiascreeningby pages 1-2)
References
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