Thalassemia: what does it mean to you?

I change this post as I discover new things, wrong things, more interesting things, etc. BEWARE if you don’t like the world dynamic.

Recently I signed a petition that asks the government (specifically, Jagat Prakash Nadda, Minister of Health and Family Welfare) to make sure that thalassemic patients who have to undergo frequent blood transfusions get sufficient supplies of Desferal, a drug that is critically important in their treatment. Desferal, manufactured by the pharmaceutical company Novartis, has been in short supply and reportedly, this problem has become acute during the past month in India.

The petition I signed said that “As of now, the company has solved the problem by making supply available.” This statement seems to support a claim made elsewhere that “Despite the company claiming that they have enough stocks, it seems an artificial shortage has been created.” And then, two days later, Novartis responded to the petition by making available sufficient supplies. WELL!

I had recently spoken to my evolutionary biology class about sickle cell disease (related to thalassemia in that both affect the functioning of haemoglobin in blood).

It is the classic case in which heterozygotes persist in the population despite the possibility that the double recessive genotype could be fatal and are expected to be selected against (see below).

The medical social issue struck me with particular force — one rarely speaks about the lives of people involved in case studies we might present in class.

What is Thalassemia?

Red blood cells (RBCs) contain haemoglobin, a protein, which binds with oxygen. Bound oxygen is carried to different parts of the body. Normal RBCs are almost spherical in outline, as on right in the figure below. via Wikipedia

If haemoglobin is damaged it may result in sickle-shaped red blood cells (the single cell on left) and it cannot do its job well. This can lead to the disease conditions thalassemia minor or, most severely, thalassemia major. The type of condition developed depends upon how much of the person’s haemoglobin is affected.

Haemoglobin protein in the blood occurs in clusters of four subunits–two units of alpha-globin (A) and two of beta-globin (B). In thalassemia major, a severe form of the disease common in India, both beta-globin units are damaged (the double recessive genotype mentioned above).

How does Thalassemia develop?

Each haemoglobin protein subunit in the blood is made by the alpha-globin gene HBA (which codes for the alpha-globin protein), or the beta-globin gene HBB (which codes for the beta-globin protein).

Each gene consists of two versions (=alleles) — one comes from your mother and the other from your father. If the alleles of both HBA and HBB (i.e., all four versions) are normal, then all is well. If even one of the alleles (of say HBB) is damaged, then it will affect the haemoglobin formed by that gene; if both alleles are affected, then a more severe form of the disease results.

How is Thalassemia transmitted?

As I said above, sickle cell anaemia has for long been an example of how heterozygotes (persons who carry one normal beta-globin allele and one damaged version) can have an advantage over homozygotes (persons who carry two normal alleles) under certain circumstances (presence of malaria).

Inheritance of Thalassemia. Source:

However, simple stories are not always as simple as they seem. The genetics of haemoglobin is not very simple, either. There are multiple copies of globin genes in humans, the sickle cell allele of HBB is only one of several alleles, and  the story of alpha-globin and beta-globin genes is turning out to be quite complex.

Where in the world does Thalassemia occur?

One variant of the disease, sickle cell anaemia, due to the beta-globin allele that causes “sickling” of RBCs, mainly occurs in Africa, West and South Asia.

Sickle Cell Distribution. Attribution: Muntuwandi at English Wikipedia via Wikipedia Commons

Persons who carry one damaged version (and one normal: heterozygotes) are less susceptible to malaria. This feature explains the persistence of the damaged beta-globin allele in the population, even though the severity of the disease means that the allele is expected to disappear over time. This *long-discussed connection between the sickle cell gene and malaria was recently investigated by detailed comparisons of the geographical occurrences of the two diseases.

Other alleles follow other geographic patterns.

*Link to a  very interesting history of this hypothesis by J. Lederberg (1999). J. B. S. Haldane (1949) informally proposed such a link for thalassemia; A. C. Allison independently (1954)  and empirically showed this for the sickle cell disease.

The connections among the genotype (genetic make-up), the phenotype (physical manifestation), the progression and treatment of the disease are complex and make their effects felt in diverse ways. Unusually, this past week, these interactions came together in my consciousness (via teaching, the news and the social media — and I just had to comment on it.

In writing this blog, I found quite a lot of misinformation, and confusing and incomplete information about the disease and its genetics on the internet. I have tried to verify what I say, and hope that in simplifying it I have not mis-stated things. Please do comment here if there is something that does not quite sound right to you. Thanks!


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One Response to Thalassemia: what does it mean to you?

  1. rgeeta says:

    If you wonder about Novartis in all this, all I can say is that:
    This is what a blog by pharmacists has to say “Novartis discontinued Desferal 2 gram vials in 2015. The 500 mg vials are available.”

    From what I can make out from a Novartis post about the dosage and administration of Desferal, the drug seems to be used in large enough quantities that 500 gm vials might be constraining. I do not know, and would welcome comments on this, especially as to whether the size of vials supplied contributed to the shortage experienced.

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