Beta thalassemia is a genetic disorder where
there’s a deficiency in production of the β-globin chains of hemoglobin, which is the
oxygen-carrying protein in red blood cells – or RBCs for short. Beta thalassemia is most
commonly seen in Mediterranean, African and South East Asian populations. Normally, hemoglobin is made up of four globin
chains, each bound to a heme group. There are four major globin chain types – alpha
(α), beta (β), gamma (γ), and delta (δ). These four globin chains combine in different
ways to give rise to different kinds of hemoglobin. First, there’s hemoglobin F (or HbF), where
F stands for fetal hemoglobin, and it’s made up of two α-globin and two γ-globin
chains. Hemoglobin A (or HbA), the major adult hemoglobin form, is made up of two α-globin
and two β-globin chains. Finally, hemoglobin A2 (or HbA2) accounts for a small fraction
of adult hemoglobin in the blood, and it’s made up of two α-globin and two δ-globin
chains. With beta thalassemia, there’s either a
partial or complete β-globin chain deficiency, due to a point mutation, which is when a single
nucleotide in DNA is replaced by another nucleotide, in the beta globin gene present on chromosome
11. And most often, these mutations occur in two regions of the gene called the promoter
sequences and splice sites, which affects the way the mRNA is read. The result is either
a reduced, or completely absent beta globin chain synthesis. And since this is an autosomal recessive disease,
two mutated copies of the gene, one from each parent, are needed to develop the disease.
If the person has just one mutated gene that codes for either a reduced production or absent
production of beta globin chains, then they have beta thalassemia minor. If the person
has two mutated genes that code for reduced beta globin chain synthesis, then they’re
said to have beta thalassemia intermedia. If the person has two β0 mutations then no
beta globin chains are produced, and they’re said to have beta thalassemia major. When there’s a β-globin chain deficiency,
free α-chains accumulate within red blood cells, and they clump together to form intracellular
inclusions, which damage the red blood cell’s cell membrane. This causes hemolysis, or red
blood cells breakdown in the bone marrow; or extravascular hemolysis, when red blood
cells are destroyed by macrophages in the spleen. Hemolysis causes hemoglobin to spill
out directly into the plasma, where heme is recycled into iron and unconjugated bilirubin.
Over time, the excess unconjugated bilirubin leads to jaundice, and excess iron deposits
leads to secondary hemochromatosis. At the same time, hemolysis leads to hypoxia,
because there are fewer red blood cells to carry oxygen to organs and tissues. And a
consequence of hypoxia is that it signals the bone marrow, and extramedullary tissues
like the liver and spleen, to increase red blood cell production, which may cause bone
marrow containing bones, like those in the skull and face, as well as the liver and spleen,
to enlarge. Ok, now, beta thalassemia minor is usually
asymptomatic. On the other hand, with beta thalassemia major, symptoms do not develop
in until the first 3 to 6 months of life. That’s because during the first 3 to 6 months
of life, fetal hemoglobin is still produced, and that process uses up some of the free
α-chains. Common beta thalassemia major signs and symptoms include symptoms of anemia like
pallor, shortness of breath, and easy fatigability; jaundice, swollen abdomen due to an enlarged
liver and spleen, hepatosplenomegaly; and growth retardation. Complications due to hemochromatosis
include arrhythmias, pericarditis, cirrhosis, hypothyroidism and diabetes mellitus. Other beta thalassemia major findings may
include enlarged forehead and cheek bones, which is called a chipmunk facies. On a skull
X-ray, the skull bones show a radiolucent bone marrow with fine, hair-like projections,
that look a bit like how the hair on your arms stands up when you get goosebumps, so
it’s called a ‘hair-on-end’ appearance. Alternatively, this is also called a crew-cut
appearance, named after a type of haircut. Diagnosis of beta thalassemia usually begins
with a routine blood test that shows a low hemoglobin levels, decreased mean corpuscular
volume or MCV, and a high red blood cell distribution width, or RDW, which indicates that red blood
cells come in a lot of different sizes. However, the RDW is often normal with beta thalassemia
minor. The peripheral blood smear shows microcytic, or small, and hypochromic, or pale, red blood
cells. There are also target cells, which are small red blood cells that look like bullseyes
due to scrunching up of the excess cell membrane. Lab work may also show high serum iron, high
ferritin, and a high transferrin saturation level. Finally, the diagnosis is confirmed
with hemoglobin electrophoresis, which shows low amounts of HbA, but an increase in HbF
and HbA2 levels, which are formed when excess α-chains start binding to γ- and δ-chains.
In beta-thalassemia minor, there’s usually an increased HbA2 level greater than 3.5%
on gel electrophoresis. Beta thalassemia minor usually doesn’t require
any treatment. Depending on hemoglobin levels, treatment of anemia in beta thalassemia major
and sometimes, intermedia, includes periodic blood transfusions. But, keep in mind that
regular blood transfusions add up to the iron overload, which can worsen hemochromatosis.
To prevent this, iron chelating agents like deferoxamine are given, which trap some of
the excess iron and sweep it away through feces or urine. Finally, a splenectomy can
be done when splenomegaly causes excess hemolysis. All right, as a quick recap… Beta thalassemia
is an autosomal recessive disorder caused by a mutation in the beta globin gene present
on chromosome 11, which results in a reduced (β+), or completely absent (β0) beta globin
chain synthesis. There are three types- beta thalassemia minor, intermedia and major. Beta-thalassemia
major causes causes chipmunk facies, ‘hair-on-end’ appearance on skull X-ray, hepatosplenomegaly,
jaundice, and secondary hemochromatosis.

16 thoughts on “Beta Thalassemia – causes, symptoms, diagnosis, treatment, pathology”

  1. Wow, right this instance I'm studying beta thalassemia! Thankss a lot for the video I'm looking forward to more of your interesting and creative expalation! β™₯οΈπŸ’ž

  2. My husband has Beta Thalassemia Minor but has some symptoms such as anemia and exhaustion. He can't give blood because he is always just a smidge below the required level. Mother in law has it too but she is completely asymptomatic. Funny thing is both are white af.

  3. She was kind of fast. I like the male narrator better. His voice is much clearer. But overall it was informative and helped a lot in understanding the topic. Thanks osmosis.

  4. I had bheta thallasemia. I use get a blood transfer once every month, getting 2 bags of blood donated.

    About 10 years ago i got a chemo therapy to undergo a bone marrow transplantation transplantation.

    The donor was my aunt.

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