Hemoglobinopathy

Hemoglobinopathy Main page
Overview
Classification
Epidemiology and Demographics
Diagnostic approach

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Overview

Hemoglobinopathy is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Most common hemoglobinopathies include sickle-cell disease and thalassemia. The hemoglobinopathies can be broadly divided into quantitative or qualitative defects. The clinical manifestations of the hemoglobinopathies ranges from mild hypochromic anemia to severe hematological disease.

Classification

Hemoglobinopathy can be classified according to genetic and structure of hemoglobin into two main groups:

Hemoglobinopathy classification

Quantititive disorders of globulin chain synthesis

Qualitative disorders of globulin structure

α-thalassemia

β-thalassemia

De novo and acquired α-thalassemia

Sickle cell disorders

Hemoglobins with decreased stability (unstable hemoglobin variants)

Hemoglobins with altered oxygen affinity

Methemoglobin

Posttranslational modifications

Deletion of α globin • One gene: α+ athalassemia • Two gene in cis: α0 thalassemia • two gene in trans: homozygous α+ thalassemia (phenotype α0 thalassemia) • Three gene: HbH disease • Four genes: Hydrops fetalis with Hb Bart's

α-Thalassemia with mental retardation syndrome (ATR): • Due to large deletions on chromosome 16 involving the α-globin genes • Due to mutations of the ATRX transcription factor gene on chromosome X • α-Thalassemia associated with myelodysplastic

SA, sickle cell trait

Mutants causing congenital Heinz body hemolytic anemia

High/increased oxygen affinity stateso • Fetal red cells • Decreased RBC 2,3 BPG • Carboxyhemoglobinemia, HbCO • Structural variants

Congenital methemoglobinemia • Structural variants • Cytochrome b5 reductase deficiency

Nonenzymatic glycosylation

Low/decreased oxygen affinity states • 2,3 BPG • Structural variants

Acquired (toxic) methemoglobinemia

Amino-terminal acetylation

Nondeletion mutants • Hb Constant Spring • Other

α-Thalassemia associated with myelodysplastic syndromes (ATMDS) • Due to mutations of the ATRX gene

SS, sickle cell anemia/disease

Acquired instability—oxidant hemolysis • Drug-induced • G6PD deficiency

Amino-terminal carbamylation

SC, HbSC disease

Deamidation

S/β thal, sickle β-thalassemia disease

S with other Hb variants: D, O-Arab, other

SF, Hb S/HPFH

Clinical classification

Biochemical/genetic classification

Structural variants with β-thalassemia phenotype

Minor/trait

Intermediate

Major

β0 thalassemia

β0 thalassemia

δ-thalassemia

γ-thalassemia

Lepore fusion gene

HbS/β-thalassemia

HbE/β-thalassemia

Other

δβ-thalassemia

εγδβ-thalassemia

HPFH

The range of clinical manifestations of the hemoglobinopathies are from mild hypochromic anemia to moderate hematological disease to severe.

Epidemiology and Demographics

Prevalence

• In 2008, the prevalence of hemoglobinopathy carrier was estimated to be 700 per 100,000 (7%), worldwide.
• The most prevalence of hemoglobinopathy gene carriers in the world's are in South-East Asia (up to 70%) and Arab nations (up to 60%).
• In Russia, prevalence of hemoglobinopathy is rare.
• In recent years, prevale of hemglobinopathy is increased in Germany.

Region

α-thalassemias

It occurs frequently in Africa, Arab nations, South-East Asia.

β-thalassemias

It occurs frequently in Mediterranean countries, South-East Europe, Arab nations, and Asia.

Diagnostic Approach

Hemoglobin testing (hemoglobin electrophoresis or chromatography), [[Red blood cell |red blood cell]] count, hemoglobin pattern, cardinal symptoms are used to reach the diagnosis of a particular hemoglobinopathy.

History & clinical symptoms

Blood test

Hemolysate

Diagnosis of abnormal hemoglobins

Diagnosis of β-thalassemia

Diagnosis of α-thalassemia

Alkaline electrophoresis • acid Electrophoresis •HPLC

Electrophoresis HPLC • HbA2,Hbf

Electrophoresis HPLC • DNA testing

Evidence of abnormality,comparison of mobility with that of known abnormalities, if HBS suspected: solubility test

Separation/quantification

Evalution of all data and findings

Evalution of all data and findings

Diagnosis of β-thalassemia

Diagnosis of α-thalassemia

DNA sequencing if needed

DNA sequencing if needed(thalassemia major, thalassemia intermedia

Evaluation of all data and findings(including blood count ethnic and origin

Diagnosis of hemoglobinopathy

References

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