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Cited by 508Hemoglobinopathies and Related DisordersHemoglobin structure and functionIron Metabolism and Disorders

α-thalassaemia

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Harteveld, Cornelis L, Higgs, Douglas R·2010·Orphanet Journal of Rare Diseases
DOI 10.1186/1750-1172-5-13PMC PMC2887799
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Abstract

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia.It is probably the most common monogenic gene disorder in the world and is especially frequent in Mediterranean countries, South-East Asia, Africa, the Middle East and in the Indian subcontinent. During the last few decades the incidence of alpha thalassaemia in North-European countries and Northern America has increased because of demographic changes. Compound heterozygotes and some homozygotes have a moderate to severe form of alpha thalassaemia called HbH disease. Hb Bart's hydrops foetalis is a lethal form in which no alpha-globin is synthesized. Alpha thalassaemia most frequently results from deletion of one or both alpha genes from the chromosome and can be classified according to its genotype/phenotype correlation. The normal complement of four functional alpha-globin genes may be decreased by 1, 2, 3 or all 4 copies of the genes, explaining the clinical variation and increasing severity of the disease. All affected individuals have a variable degree of anaemia (low Hb), reduced mean corpuscular haemoglobin (MCH/pg), reduced mean corpuscular volume (MCV/fl) and a normal/slightly reduced level of HbA2. Molecular analysis is usually required to confirm the haematological observations (especially in silent alpha-thalassaemia and alpha-thalassaemia trait). The predominant features in HbH disease are anaemia with variable amounts of HbH (0.8-40%). The type of mutation influences the clinical severity of HbH disease. The distinguishing features of the haemoglobin Bart's hydrops foetalis syndrome are the presence of Hb Bart's and the total absence of HbF. The mode of transmission of alpha thalassaemia is autosomal recessive. Genetic counselling is offered to couples at risk for HbH disease or haemoglobin Bart's Hydrops Foetalis Syndrome. Carriers of alpha+- or alpha0-thalassaemia alleles generally do not need treatment. HbH patients may require intermittent transfusion therapy especially during intercurrent illness. Most pregnancies in which the foetus is known to have the haemoglobin Bart's hydrops foetalis syndrome are terminated due to the increased risk of both maternal and foetal morbidity.

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  • The GAP-PCR was specifically designed to identify the common α-thalassemia deletions.

    “Secondly, the GAP-PCR was specifically designed to identify the common α-thalassemia deletions, and the strip-assay methods can detect approximately 90% of α-thalassemia gene mutations (8,37).”

    From Machine Learning-Based Prediction of Hemoglobinopathies Using Complete Blood Count Data (2024) · cites this paper as [8]

  • The strip-assay methods can detect approximately 90% of α-thalassemia gene mutations.

    “Secondly, the GAP-PCR was specifically designed to identify the common α-thalassemia deletions, and the strip-assay methods can detect approximately 90% of α-thalassemia gene mutations (8,37).”

    From Machine Learning-Based Prediction of Hemoglobinopathies Using Complete Blood Count Data (2024) · cites this paper as [8]

    The Molecular analysis section describes gap-PCR, sequencing and MLPA, but does not address strip-assay detection rates. Searches for strip assays and the approximately 90% figure found no passage supporting that claim. (LLM, conf=0.74)

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Cited by

Sorted by citations

Authors
Harteveld, C. L., & Higgs, D. R.
Affiliations
  • Leiden University Medical Center (NL)
  • John Radcliffe Hospital (GB)
Corresponding author
Higgs, Douglas R
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2010-05-28
Volume
5
Issue
1
Pages
13-13
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/1750-1172-5-13
PMC
PMC2887799
OpenAlex
W4211199099
Cited by
508
References
0
Citations by year
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FWCI
2.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
alpha-thalassemia, Hb H disease, alpha-globin gene deletion, microcytic hypochromic anemia, genotype-phenotype correlation, autosomal recessive inheritance, genetic counseling, prenatal termination, HbA2
MeSH terms
Hemoglobins, Abnormal, Humans, Mutation, alpha-Thalassemia, Gene Deletion, alpha-Globins

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