Alpha ThalassemiaBy:b.Sadeghi2008

Alpha thalassemiaThe thalassemias are the commonest single

gene disorders.The thalassemias are a hetrogeneous group of genetic disorders of haemoglobin synthesis

which result from a reduced rate of production of one or more of the globin

chains of haemoglobin.Heterozygotes are usually symptomles.Clinically are classified according to their

severity in to major,minor,intermedia.

Alpha thalassemia Distribution:sub saharan africa,middle

east,mediterranean region.Genetic disorders of Alpha-chain synthesis result in

defective fetal (Hb F) and adult (Hb A) production.In fetus:deficiency of Alpha -chains result in

production of exess Gama-chains (Hb Bart).In adult: deficiency of Alpha-chains result in

production of exess Beta-chains (Hb H).

Alpha thalassemia

Molecular pathology α0-thalassemia:Results from deletions of both α-globin genes.Result from deletions a bout 40 kb up stream

from the α-globin gene cluster. α+-thalassemia:Results from deletions that remove one of the

linked pairs of α-globin genes leaving the other one intact.

Both α-globin genes are intact but one of them has a mutation that either partially or completely inactivates.

pathophysiology Deficiency of α -chains leads to the

production of excess γ or β chains. These soluble tetramers (γ4 , β4 )do not

percipitate extensively in the bone marrow ,erythropoisis is more effective than in β-thalassemia.

Hb Bart ,Hb H have a very high oxygen affinity.

Hydrops syndrome Follow the homozygous inheritance

of α0 thalasemmia. There is no production of α-

chains(neither fetal nor adult) Hb bart :%80 Hb portland:

%20 This syndrome characterized by: Fetal death High incidence of toxaemia of

pregnancy. Obstetric complications(large

placenta)

Hb H diseaseMost forms due to the coinheritanse of α0 and α+ thalassemia.May due to inheritanse of α0 -thalassemia and Hb constant spring.Hb H is unstable and precipitate in red cells.Patients usually survive in to adult life.Hb H : % 5- % 40Golf body:brilliant cresyl blue.

Alpha thalassemia traitMild hypochromia anemia.Hb A2 is normal.Hb Bart :% 5-6 α/β =0.6 DNA analysis for certain diagnosis.

Silent carrier:No clinical or hematological abnormality.

ATR - 16•Encoded on chromosom 16 .

•Results from the loss of two megabase from the subtelomereric end of the short arm of chromosom 16.

•Children have a mild degree of mental retardation and no dismorphic feature.

ATR - X

Encoded on x chromosom.

Children have severe mental disorder.

Results from many diffrent mutations of the ATR X gene.

Molecular diagnosis

Almost all method for DNA analysing of the hemoglobinopathies used are based on the PCR .

The PCR based technique used in hemoglobin diagnosis:Allel spesific oligonuclotid (ASO).Reverse dot blot analysing.Restriction enzyme analysis.Amplification refractory mutation

system(ARMS)Hybridization.Gap – PCR.

Other techniques:

Direct sequence analysing.

Suthern blot.

The α/β globin ratio.

Fetal DNA analysing For prenatal diagnosis.

Sample(chronic villus in trimester pregnancy).

PCR thechniques