Hemoglobinopathy
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Hemoglobinopathy Main page |
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.The renge of clinical manifestations of the hemoglobinopathies are from mild hypochromic anemia to moderate hematological disease to severe.
Classification
Hemoglobinopathy be classified according to genetic and structure of hemoglobin into two main groups:
- Thalassemia syndromes
- α-thalassemia
- β-thalassemia
- Structural hemoglobin variants
- HbS
- HbE
- HbC
- Hb Bart’s
- Hb J(Johnstown)
- HbM
- HbX
- HbD
| Hemoglobinopathy classification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Quantititive disorders of globin chain synthesis | Qualitative disorder of globin 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+ thalassemia • 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 states • 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 • Increased RBC 2,3 BPG • Structural variants | Acquired (toxic) methemoglobinemia | Amino-terminal acetylation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nondeletion mutants • Hb Constnt 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.
Differentiating between Hemoglobinopathies
| Gene type | Red blood cell (RBC) count g/dl | Hemoglobin pattern | Differentiating Symptoms | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Hemoglobin g/dl | MCH /pg | Hemoglobinpattern | ||||||||
| Alpha Thalassemia | -+/++ | Normal | Normal | Normal | Normal | None | ||||
| -+/-+
--/++ |
Normal or low | <26 | Normal | Normal | Mild anemia | |||||
| --/-+ | 8 to 10 | <22 | HbH &asymp
10 to 20% |
HbH 10 to 20% | Chronic hemolytic anemia | |||||
| Hb Bart’s hydrops fetalis
--/-- |
<6 | <20 |
|
Hb Bart’s 80 to 90%,
Hb Portland 10 to 20%, HbH <1% |
Life-threatening fetal anemia | |||||
| β-thalassemia | Heterozygous | &β/++ | 9 to 15 | HbA2 >3.2% | ||||||
| &β/+- | HbF 0.5 to 6% | |||||||||
| &β/-- | 19 to 25 | |||||||||
| Compound heterozygous | β + /β 0 | |||||||||
| Homozygous | β+/β+ | <7 | ||||||||
| β 0 /β 0 | ||||||||||
| Sickle cell Disease | 6 to 9 | |||||||||
| HBC | ||||||||||
Epidemiology and Demographics
Incidence
- The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
- In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.[1]
Prevalence
- In 2008, the prevalence of hemoglobinopathy was estimated to be 7% of the worldwide population being carrier.[1]
- The most prevalance of hemoglobinopathy gene carriers in the world's are in South-East Asia(up to 70%) and Arab nations(up to 60).[1]
- In Russia is seen rare[1]
- Recent years is increased in Germany.[2]
Race
α-thalassemias
It occure cur mainly in Africa, Arab nations, and, more frequently and South-East Asia.
β-thalassemias
It occure cur mainly in Mediterranean countries, South-East Europe, Arab nations and Asia.
Diagnosis
Hemoglobin testing(hemoglobin electrophoresi or chromatography) , red blood cell count, hemoglobin pattern, cardinal symptoms[3]
| Hemoglobinopathy | |||||||||||||||||||||||||||||||||||
| History & clinical symptoms | |||||||||||||||||||||||||||||||||||
| Hemolystate | Blood count, including RBC morphology | ||||||||||||||||||||||||||||||||||
| Diagnosis of abnormal hemoglobin | Diagnosis of β-thalassemia | Diagnosis of α-thalassemia | |||||||||||||||||||||||||||||||||
References
- ↑ 1.0 1.1 1.2 1.3 Kohne E (August 2011). "Hemoglobinopathies: clinical manifestations, diagnosis, and treatment". Dtsch Arztebl Int. 108 (31–32): 532–40. doi:10.3238/arztebl.2011.0532. PMC 3163784. PMID 21886666.
- ↑ Cario H, Stahnke K, Sander S, Kohne E (January 2000). "Epidemiological situation and treatment of patients with thalassemia major in Germany: results of the German multicenter beta-thalassemia study". Ann. Hematol. 79 (1): 7–12. PMID 10663615.
- ↑ Herklotz R, Risch L, Huber AR (January 2006). "[Hemoglobinopathies--clinical symptoms and diagnosis of thalassemia and abnormal hemoglobins]". Ther Umsch (in German). 63 (1): 35–46. doi:10.1024/0040-5930.63.1.35. PMID 16450733.