Користувач:Aspilemetala/Чернетка/Таласемія

Патофізіологія

У здорової людини зазвичай гемоглобін A складається з 4 бількових ланцюгів, двох α- і двох β-глобінових ланцюгів, організованих у гетеротетрамер. При таласемії пацієнти мають дефекти в α- або β-глобінових ланцюгах, яки спричиняють вироблення анормального гемоглобіну^{[джерело?]}.

Таласемії класифікуються залежно від того, який ланцюг молекули гемоглобіну уражений. In α-thalassemias, production of the α-globin chain is affected, while in β-thalassemia, production of the β-globin chain is affected.

The β-globin chains are encoded by a single gene on хромосома 11 (людина); α-globin chains are encoded by two closely linked genes on хромосома 16 (людина). Thus, in a normal person with two copies of each chromosome, two loci encode the β chain, and four loci encode the α chain. Deletion of one of the α loci has a high prevalence in people of African or Asian descent, making them more likely to develop α-thalassemia. β-Thalassemias are not only common in Africans, but also in Греки, Turks and Італійці.^{[джерело?]}

Alpha-thalassemias

The α-thalassemias involve the genes HBA1 and HBA2, inherited in a Mendelian recessive fashion. Two gene loci and so four alleles exist. Two genetic loci exist for α-globin, thus four alleles are in diploid cells. Two alleles are maternal and two alleles are paternal in origin. The severity of the α-thalassemias is correlated with the number of affected α-globin; alleles: the greater, the more severe will be the manifestations of the disease. Alpha-thalassemias result in decreased alpha-globin production; therefore, fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers (called hemoglobin H or HbH of 4 beta chains), which have abnormal oxygen dissociation curves. Alpha thalassemias often are found in people from Southeast Asia, the Middle East, China, and in those of African descent.

# of missing alleles	Types of alpha thalassemia	Symptoms
1	Silent carrier	No symptoms
2	Alpha thalassemia trait	Minor anemia
3	Hemoglobin H disease	Mild to moderate anemia; may lead normal life
4	Hydrops fetalis	Death usually occurs in utero or at birth

Beta-thalassemia

Beta thalassemias are due to mutations in the HBB gene on chromosome 11, also inherited in an autosomal, recessive fashion. The severity of the disease depends on the nature of the mutation and on the presence of mutations in one or both alleles.
Mutated alleles are called β⁺ when partial function is conserved (either the protein has a reduced function, or it functions normally but is produced in reduced quantity) or β^o, when no functioning protein is produced.
The situation of both alleles determines the clinical picture:

• β thalassemia major (Mediterranean anemia or Cooley anemia) is caused by a β^o/β^o genotype. No functional β chains are produced, and thus no hemoglobin A can be assembled. This is the most severe form of β-thalassemia;
• β thalassemia intermedia is caused by a β⁺/β^o or β⁺/β⁺ genotype. In this form, some hemoglobin A is produced;
• β thalassemia minor is caused by a β/β^o or β/β⁺ genotype. Only one of the two β globin alleles contains a mutation, so β chain production is not terribly compromised and patients may be relatively asymptomatic.

Beta thalassemia most often occurs in people of Mediterranean origin. To a lesser extent, Chinese, other Asians, and African Americans can be affected.

Delta-thalassemia

As well as alpha and beta chains present in hemoglobin, about 3% of adult hemoglobin is made of alpha and delta chains. Just as with beta thalassemia, mutations that affect the ability of this gene to produce delta chains can occur.

Combination hemoglobinopathies

Thalassemia can coexist with other hemoglobinopathies. The most common of these are:

• Hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts of India, it is clinically similar to β thalassemia major or thalassemia intermedia.^{[джерело?]}
• Hemoglobin S/thalassemia: common in African and Mediterranean populations, is clinically similar to sickle-cell anemia, with the additional feature of splenomegaly.^{[джерело?]}
• Hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/β^o thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β⁺ thalassemia produces a milder disease.^{[джерело?]}
• Hemoglobin D/thalassemia: common in the northwestern parts of India and Pakistan (Punjab region).