   #copyright

Thalassemia

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Thalassemia
   Classifications and external resources

   ICD- 10 D 56.
   ICD- 9  282.4

   Thalassemia (American English) or thalassaemia (British English) is an
   inherited disease of the red blood cells. In thalassemia, the genetic
   defect results in reduced rate of synthesis of normal globin
   chains(c.f. hemoglobinopathy which is a structural change in a globin
   chain leading to instability or abnormal with the Mediterranean
   seaamong different populations.

Classification

   The thalassemias are classified according to which chain of the globin
   molecule is affected: in α thalassemia, the production of α globin is
   deficient, while in β thalassemia the production of β globin is
   defective. Thalassemia produces a deficiency of α or β globin, unlike
   sickle-cell disease which produces a specific mutant form of β globin.

Prevalence

   The estimated prevalence is 16% in people from Cyprus, 3-14 % in
   Thailand, and 3-8 % in populations from India, Pakistan, Bangladesh,
   and China. A lower prevalence has been reported from black people in
   Africa (0.9%) and northern Europe (0.1%).(4)

Alpha (α) thalassemias

   The alpha thalassemias involve the genes HBA1 ( Mendelian Inheritance
   in Man (OMIM) 141800) and HBA2 ( Mendelian Inheritance in Man (OMIM)
   141850), inherited in a Mendelian recessive fashion. It is also
   connected to the deletion of the 16p chromosome. α thalassemias result
   in excess β chain production in adults and excess γ chains in newborns.
   The excess β chains form unstable tetramers that have abnormal oxygen
   dissociation curves.

   There are four genetic loci for α globin. The more of these loci that
   are deleted or affected by mutation, the more severe will be the
   manifestations of the disease:
     * If all four loci are affected, the fetus cannot live once outside
       the uterus: most such infants are dead at birth with hydrops
       fetalis, and those who are born alive die shortly after birth. They
       are edematous and have little circulating hemoglobin, and the
       hemoglobin that is present is all tetrameric γ chains (hemoglobin
       Barts). Usually, this involves homozygous inheritance of an alpha
       thalassemia trait, type 1.
     * If three loci are affected, Hemoglobin H disease results. Two
       unstable hemoglobins are present in the blood, both hemoglobin
       Barts (tetrameric γ chains) and hemoglobin H (tetrameric β chains).
       There is a microcytic hypochromic anaemia with target cells and
       Heinz bodies (precipitated Hb H) on the peripheral blood smear. The
       disease may first be noticed in childhood or in early adult life,
       when the anaemia and splenomegaly are noted. This is usually due to
       compound heterozygous inheritance of alpha thalassemia type 1 and
       type 2 traits.
     * If two of the four α loci are affected, alpha thalassemia trait,
       type 1 results. Two α loci permit nearly normal erythropoiesis,
       though there is a mild microcytic hypochromic anaemia. There is a
       high prevalence (about 30%) of deletion of one of the two α loci on
       chromosomes of people of recent African origin, and so the
       inheritance of two such chromosomes is not uncommon. The disease in
       this form can be mistaken for iron deficiency anaemia and treated
       inappropriately with iron. Two modes of alpha thalassemia trait,
       type 1 has been noted. One involves cis deletion of two alpha loci
       on the same chromosome; another involves trans deletion of
       allelelic genes on homologous chromosomes (no. 16).
     * If one of the four α loci is affected, alpha minor or alpha+
       thalassemia trait or alpha thalassemia trait, type 2 results and
       there is minimal effect. Three α-globin loci are enough to permit
       normal hemoglobin production, and there is no anaemia or
       hypochromia in these people. They have been called α thalassemia
       carriers.

Beta (β) thalassemias

   Beta thalassemia (also known as Cooley's Anaemia) is due to mutations
   in the HBB gene on chromosome 11 ( Mendelian Inheritance in Man (OMIM)
   141900), also inherited in a Mendelian recessive fashion. In β
   thalassemia, excess α chains are produced, but these do not form
   tetramers: rather, they bind to the red blood cell membranes producing
   membrane damage, and at high concentrations have the tendency to form
   toxic aggregates. The severity of the damage depends on the nature of
   the mutation. Some mutations (β^o) prevent any formation of β chains;
   others (β^+) allow some β chain formation to occur. Recently,
   increasing reports suggest that up to 5% of patients with
   beta-thalassemias produce fetal hemoglobin (HbF), and use of
   hydroxyurea also has a tendency to increase the production of HbF, by
   as yet unexplained mechanisms.

   Any given individual has two β globin alleles:
     * If both have thalassemia mutations, a severe microcytic,
       hypochromic anaemia called β thalassemia major or Cooley's anaemia
       results. Untreated, this results in death before age twenty:
       treatment consists of periodic blood transfusion; splenectomy if
       splenomegaly is present, and treatment of transfusion-caused iron
       overload. Cure is possible by bone marrow transplantation.
     * If only one β globin allele bears a mutation, β thalassemia minor
       results (sometimes referred to as β thalassemia trait). This is a
       mild anaemia with microcytosis. Symptoms include weakness and
       fatigue - in most cases β thalassemia minor may be asymptomatic and
       many people may be unaware they have this disorder. Detection
       usually involves counting the mean corpuscular volume (size of red
       blood cells) and noticing a slightly decreased mean volume than
       normal.
     * Thalassemia intermedia is a condition intermediate between the
       major and minor forms. Sufferers can often manage a normal life but
       may need occasional transfusions e.g. at times of illness or
       pregnancy. This really depends on the severity of their anaemia.

   The actual genetic cause of β thalassemias are actually very diverse
   and a number of different mutations can cause reduced or absent β
   globin synthesis. Usually, superscripts 0 and + are added to β to
   indicate complete absence, and deficient synthesis of β globins
   respectively.

   Mainly there are two forms of genetic defects which produce β
   thalassemias:
     * Nondeletion forms: These defects generally involve a single base
       substitution or small deletion or inserts near or upstream of the β
       globin gene. Most commonly, mutations occur in the promoter regions
       preceding the beta-globin genes. Less often, abnormal splice
       variants are believed to contribute to the disease.
     * Deletion forms: Deletions of different sizes involving the β globin
       gene produce different syndromes such as (β^o) or hereditary
       persistence of fetal hemoglobin syndromes.

Delta (δ) thalassemia

   As well as alpha and beta chains being present in hemoglobin about 3%
   of adult hemoglobin is made of alpha and delta chains. The gene for
   delta chains is very close to the gene for beta hemoglobin and damage
   to this gene can also affect the beta chain gene, thus delta
   thalassemia is usually very similar in effect to Beta thalassemia.

In combination with other hemoglobinopathies

   Thalassemia can co-exist with other hemoglobinopathies. The most common
   of these are:
     * hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts
       of India; clinically similar to β thalassemia major or thalassemia
       intermedia.
     * hemoglobin S/thalassemia, common in African and Mediterranean
       populations; clinically similar to sickle cell anaemia, with the
       additional feature of splenomegaly
     * hemoglobin C/thalassemia: common in Mediterranean and African
       populations, hemoglobin C/β^o thalassemia causes a moderately
       severe hemolytic anaemia with splenomegaly; hemoglobin C/β^+
       thalassemia produces a milder disease.

Treatment and complications

   Anyone with thalassemia should consult a properly qualified
   hematologist.

   Thalassemias may co-exist with other deficiencies such as folic acid
   (or folate, a B-complex vitamin) and iron deficiency (only in
   Thalassemia Minor).

Thalassemia Minor

   Contrary to popular belief, Thalassemia Minor patients should not avoid
   iron-rich foods by default. A serum ferritin test can determine what
   their iron levels are and guide them to further treatment if necessary.
   Thalassemia Minor, although not life threatening on its own, can affect
   quality of life due to the effects of a mild to moderate anaemia.
   Studies have shown that thalassemia Minor often coexists with other
   diseases such as asthma, and even bipolar disorder.

Thalassemia prevention and management

   Autosomal recessive inheritance

   α and β thalassemia are often inherited in an autosomal recessive
   fashion although this is not always the case. Reports of dominantly
   inherited α and β thalassemias have been reported the first of which
   was in an Irish family who had a two deletions of 4 and 11 bp in exon 3
   interrupted by an insertion of 5 bp in the β-globin gene. For the
   autosomal recessive forms of the disease both parents must be carriers
   in order for a child to be affected. If both parents carry a
   hemoglobinopathy trait, there is a 25% chance with each pregnancy for
   an affected child. Genetic counseling and genetic testing is
   recommended for families that carry a thalassemia trait.

   There are an estimated 60-80 million people in the world who carry the
   beta thalassemia trait alone. This is a very rough estimate and the
   actual number of thalassemia Major patients is unknown due to the
   prevalence of thalassemia in less developed countries in the Middle
   East and Asia. Countries such as India, Pakistan and Iran are seeing a
   large increase of thalassemia patients due to lack of genetic
   counseling and screening. There is growing concern that thalassemia may
   become a very serious problem in the next 50 years, one that will
   burden the world's blood bank supplies and the health system in
   general. There are an estimated 1,000 people living with Thalassemia
   Major in the United States and an unknown number of carriers. Because
   of the rarity of the disease in countries with little knowledge of
   thalassemia, access to proper treatment and diagnosis can be difficult.

   As with other genetically acquired disorders, aggressive birth
   screening and genetic counseling is recommended for prevention of a
   world crisis.

   A screening policy exists on both sides of the island of Cyprus to
   reduce the incidence of thalassemia, which since the program's
   implementation in the 1970s (which also includes pre-natal screening
   and abortion) has reduced the number of children born with the
   hereditary blood disease from 1 out of every 158 births to almost zero.

Benefits

   Being a carrier of the disease may confer a degree of protection
   against malaria, and is quite common among people from Italian or Greek
   origin, and also in some African and Indian regions. This is probably
   by making the red blood cells more susceptible to the less lethal
   species Plasmodium vivax, simultaneously making the host RBC
   environment unsuitable for the merozoites of the lethal strain
   Plasmodium falciparum. This is believed to be a selective survival
   advantage for patients with the various thalassemia traits. In that
   respect it resembles another genetic disorder, sickle-cell disease.

   Epidemiological evidence from Kenya suggests another reason: protection
   against severe anaemia may be the advantage..

   People diagnosed with heterozygous (carrier) Beta-Thalassemia have some
   protection against coronary heart disease.

Famous people

     * Former professional tennis player Pete Sampras is known to be a
       Thalassemia minor patient.
     * Former professional football (soccer) player Zinedine Zidane is
       known to be a Thalassemia minor patient.
     * Rabbi Kohan Shalomim Y. Halahawi, Founder of the African Hebrew
       Israelite Community Ha' Yisrayli Torah Brith Yahad, and Doctor of
       Electro-homeopathic Medicine MD(AM), Edenic-Light Natural Medicine
       Research Foundation, is known to have Thalassemia B+.

   Retrieved from " http://en.wikipedia.org/wiki/Thalassemia"
   This reference article is mainly selected from the English Wikipedia
   with only minor checks and changes (see www.wikipedia.org for details
   of authors and sources) and is available under the GNU Free
   Documentation License. See also our Disclaimer.
