Genetic syndrome of ineffective erythropoiesis caused by mutations of the beta-globin gene.
Spectrum of severity from asymptomatic to severe anaemia and skeletal changes.
Blood transfusions are required for beta-thalassaemia intermedia and major, but are associated with iron overload complications.
Stem cell transplantation offers cure.
Beta-thalassaemia is an inherited microcytic anaemia caused by mutation(s) of the beta-globin gene leading to decreased or absent synthesis of beta-globin, resulting in ineffective erythropoiesis.
The genotypic spectrum includes homozygous and heterozygous defects, resulting in a phenotypic spectrum ranging from transfusion dependence to the asymptomatic carrier state.
Compound heterozygosity of beta-thalassaemia with haemoglobin E mutations results in a phenotype more severe than either beta-thalassaemia trait or haemoglobin E mutations alone, similar to beta-thalassaemia major or intermedia.
History and exam
Key diagnostic factors
- country of origin or ancestry
- family history
Other diagnostic factors
- abdominal distension
- failure to gain weight
- low height and weight
- spinal changes
- large head
- chipmunk facies
- misaligned teeth
- positive family history
1st investigations to order
- peripheral smear
- reticulocyte count
- haemoglobin analysis
- plain x-rays of skull
- abdominal ultrasonography
- plain x-rays of long bones
Investigations to consider
- genetic testing
- HLA typing
beta-thalassaemia intermedia: non-transfusion-dependent
beta-thalassaemia intermedia: transfusion-dependent
Sujit Sheth, MD
Professor of Clinical Pediatrics
Weill-Cornell Medical College
SS is a consultant for Bristol Myers Squibb (formerly Celgene), manufacturer of luspatercept; for Bluebirdbio, developer of a gene therapy product for transfusion dependent beta-thalassaemia; and for Agios, related to mitapivat for thalassaemia. Steering committee member for CTX001, gene editing product by CRISPR/Vertex. Participation in multicentre trials conducted by LaJolla, Bristol Myers Squibb, Terumo, Novartis, Dispersol. SS is also an author of references cited in this topic.
Christoph Pechlaner, MD
Associate Professor of Medicine
Innsbruck Medical University
CP declares that he has no competing interests.
Michael R. Jeng, MD
Pediatric Hematology & Oncology
Stanford University School of Medicine
MRJ declares that he has no competing interests.
- Congenital dyserythropoietic anaemia (CDA)
- Pyruvate kinase (PK) deficiency
- Mild iron deficiency anaemia
- A short guide for the management of transfusion dependent thalassaemia
- Guidelines for the management of non transfusion dependent thalassaemia, 2nd edition
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