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 0-thalassemia:Results from deletions of both -globin genes.Result from deletions a bout 40 kb up stream from the -globin gene cluster. +-thalassemia:Results from deletions that remove one of the linked pairs of -globin genes leaving the other one intact.Both -globin genes are intact but one of them has a mutation that either partially or completely inactivates.

pathophysiology Deficiency of -chains leads to the production of excess or chains. These soluble tetramers (4 , 4 )do not percipitate extensively in the bone marrow ,erythropoisis is more effective than in -thalassemia. Hb Bart ,Hb H have a very high oxygen affinity.

Hydrops syndromeFollow the homozygous inheritance of 0 thalasemmia.There is no production of -chains(neither fetal nor adult)Hb bart :%80 Hb portland:%20This syndrome characterized by:Fetal deathHigh incidence of toxaemia of pregnancy.Obstetric complications(large placenta)

Hb H diseaseMost forms due to the coinheritanse of 0 and + thalassemia.May due to inheritanse of 0 -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 / =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 / globin ratio.

Fetal DNA analysing For prenatal diagnosis.

Sample(chronic villus in trimester pregnancy).

PCR thechniques

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