Mark ở vũ trụ khác · Another Universe Genes and Rare Diseases #5 · Blood · Inheritance

Thalassemia: rare in one place, common in another

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Cooley & Lee 1925 · screening programmes in Cyprus (from 1973) and Sardinia · Vietnam today

ConditionThalassemia, an inherited disorder of haemoglobin
GenesHBB (beta chain) and HBA1, HBA2 (alpha chains)
The storytwo islands almost stopped babies being born with the severe form, by learning who carries the gene
LabelSolid, with caution on press figures

For reading and understanding, not a substitute for medical advice.

Source: GeneReviews "Beta-Thalassemia" (Langer, updated Feb 2024); Modell and Darlison (2008), Bulletin of the World Health Organization 86(6): 480–487.

Recap in 1 minute

Essence

A fault in a haemoglobin geneThe body makes too little of one of the two chains of haemoglobin, so red cells are weak and break early.
It takes a gene from both parentsIf both parents carry it, each pregnancy has a 25% chance of an affected child.
"Rare" depends on whereIn Vietnam, 13.8% of people carry a thalassemia gene, according to a 2017 national survey.
Screening worksCyprus went from 70–80 expected cases to fewer than 5 a year, by testing carriers and counselling couples.
Gene therapy existsSince 2022, most people in the trials stopped needing transfusions. The price is over 2 million US dollars.

Source: GeneReviews (Langer 2024); Bach et al. (2022), Hemoglobin 46(1): 62–65 (13.8%); Telfer et al. (2006), Haematologica (Cyprus); FDA decisions on Zynteglo (Aug 2022) and Casgevy (Jan 2024), via BioSpace and MLO; prices from US press (secondary source).

Part 1

Question

A disease that is "rare" in Europe sits in the genes of more than 13 percent of Vietnamese people. Why is a disease gene so common in some regions, and what did people do so that fewer children are born needing transfusions for life?

The question is Mark's, based on Modell and Darlison (2008) and Bach et al. (2022).

1925Naming the diseaseDoctors in Detroit see children of Mediterranean descent with severe anaemia.
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From 1973Two islandsCyprus and Sardinia test carriers and counsel couples.
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TodayVietnamPrenatal screening, premarital check-ups, and gene therapy elsewhere in the world.
Part 2

The story

Who, where, when: from a children's clinic in the US to two Mediterranean islands and Vietnam.

1925 · Detroit, USAPaediatrician Thomas Cooley and his colleague Lee describe children of Italian and Greek descent with severe anaemia, a large spleen and changes in the facial bones. The illness becomes known by his name: "Cooley's anaemia".
1930s · A name from the seaTwo doctors in Rochester (USA), Whipple and Bradford, coin "thalassemia", from the Greek thalassa, the sea, because the first cases were all children with roots around the Mediterranean.
1949 · A question about malariaGeneticist J.B.S. Haldane asks why a disease gene is so common in Italy, Sicily and Greece. He guesses that people with one copy resist malaria better, so the gene is kept over generations.
1973 · Cyprus beginsNearly 1 in 7 Cypriots carries the gene. The island starts public education, carrier testing and counselling. From 1977 prenatal diagnosis is added. Dr Minas Angastiniotis describes the programme in The Lancet in 1981.
1983 · A paper before the weddingThe Orthodox Church in Cyprus asks couples for a certificate showing they have been tested before a church wedding. Results stay confidential, and whether to marry is still the couple's choice.
Mid-1970s · Sardinia (Italy)Dr Antonio Cao's team in Cagliari finds 12.6% of people carry the gene, then starts voluntary screening with prenatal diagnosis.
Today · VietnamA 2017 national survey: 13.8% of the population carries a thalassemia gene. The National Institute of Hematology and Blood Transfusion estimates about 8,000 babies are born with the disease each year, about 2,000 with the severe form.

Source: Cooley and Lee (1925), Transactions of the American Pediatric Society, via whonamedit.com and thebloodproject.com (secondary source); sources give 1932 or 1936 for the naming; Haldane (1949), via a review on PMC (PMC3499995); Angastiniotis and Hadjiminas (1981), The Lancet 1(8216): 369–371; Telfer et al. (2006), Haematologica (about 15% carriers); Cyprus Mail, 17 Mar 2023 (1983 certificate, secondary source); Cao et al. (1978), Journal of Medical Genetics 15(6): 443 (12.6%); Bach et al. (2022), Hemoglobin 46(1): 62–65 (13.8%); births per year as stated by Dr Bach Quoc Khanh of the National Institute of Hematology and Blood Transfusion in Thanh Tra and VOV (secondary source).

Share of people carrying a gene in three places. Sardinia, 1978 survey: 12.6 percent. Cyprus: about 15 percent. Vietnam, 2017 survey: 13.8 percent. how many people carry one thalassemia gene? Sardinia (1978)12.6% Cyprusabout 15% Vietnam (2017)13.8% roughly 1 in every 7 or 8 people carries it; most do not know, because they are healthy
Three places half a world apart, the same carrier rate. In northern Europe the disease is rare. Where malaria was once common, the gene is common.Source: Cao et al. (1978), J Med Genet 15(6) (Sardinia); Telfer et al. (2006), Haematologica (Cyprus, about 15%; a 2013 review gives about 12% recently); Bach et al. (2022), Hemoglobin 46(1) (Vietnam).
In Vietnam, the rate varies widely between ethnic groups

The press, citing the National Institute of Hematology and Blood Transfusion, gives about 9.8% carriers among the Kinh majority and over 20% in some northern mountain groups (Tày 26.1%, Dao 25.5%, Nùng 24.7%). These are secondary sources, not yet checked against the original report.

The Institute team's 2022 paper also notes that rates "vary by ethnicity and topography", and that prevention relies on prenatal and newborn diagnosis.

Source: Văn hoá, Lào Cai and PLO newspapers citing the National Institute of Hematology and Blood Transfusion (secondary source); Bach et al. (2022), Hemoglobin 46(1): 62–65.

Part 3

How the gene works

1. Haemoglobin carries oxygen inside red cells and is built from four chains: two alpha and two beta. The HBB gene on chromosome 11 makes the beta chain; two genes, HBA1 and HBA2 on chromosome 16, make the alpha chain.

2. In beta-thalassemia, a faulty HBB gene makes little or no beta chain. The spare alpha chains clump together, killing young red cells in the bone marrow and making mature red cells break early: the person becomes anaemic.

3. Everyone has two copies of HBB, one from each parent. One faulty copy: a carrier, usually healthy, with slightly small red cells. Two faulty copies: the disease, and the severe form needs transfusions from 6 to 24 months of age.

Left: normal haemoglobin, two alpha and two beta chains in balance. Right: beta-thalassemia, beta chains missing, spare alpha chains clump, red cells break. normal: 2 alpha + 2 beta α β β α carries oxygen well, red cells hold up beta-thalassemia: beta missing α ? spare alpha clumps young cells die in the marrow, red cells break early
Not anaemia from lack of iron, but from a missing piece. Alpha-thalassemia is the reverse: too little alpha chain. Losing all four alpha genes is the most severe form, and the fetus usually cannot survive.Source: GeneReviews "Beta-Thalassemia" (Langer 2024) and "Alpha-Thalassemia"; MedlinePlus Genetics. Self-drawn diagram, not to scale.
Both parents carry one faulty copy. In each pregnancy: 25 percent chance the child carries no faulty copy, 50 percent chance the child is a carrier like the parents, 25 percent chance the child has the disease. father, carriermother, carrier 25%not a carrier 50%carrier, usually healthy 25%affected the odds for EACH pregnancy, not "1 in every 4 children"
Recessive inheritance: one faulty copy from each parent. Because carriers are usually healthy, many couples only find out when their first child is ill. That is why Cyprus and Sardinia test beforehand.Source: GeneReviews "Beta-Thalassemia" (Langer 2024), Genetic Counseling section; MedlinePlus Genetics "Beta thalassemia".
Part 4

Fact check: true stories and rumours

14 things people say about thalassemia, checked against medical sources. Tap a row for the reason.

Cyprus: without prevention, 70 to 80 affected births a year were expected; after the programme, fewer than 5 a year. Sardinia: the severe form went from 1 in 250 births, to 1 in 1,000, then 1 in 4,000 in 1996. Cyprus: affected births per year expected without action70–80 after the programmeunder 5 Sardinia: severe cases per births 1/250 → 1/1,000 → 1/4,000 (1996) grey bar is the old level; dark bars are after screening (same scale)
Two islands, one approach: know you carry the gene before having children.Source: Telfer et al. (2006), Haematologica (Cyprus; a 2013 review gives an expected 30–50); Rosatelli et al. (about 1990, Cagliari) (1/250 → 1/1,000); a Haematologica article citing 1/4,000 in 1996. Checked via web search, 16 Oct 2026.
SOLIDA child has the severe disease only with a faulty gene from both parents

Beta-thalassemia is autosomal recessive (GeneReviews; MedlinePlus). Dominant forms are very rare.

SOLIDIf both parents are carriers, each pregnancy has a 25% chance of an affected child

And 50% carrier, 25% non-carrier. The odds reset with every pregnancy (GeneReviews, genetic counseling).

SOLIDCarriers are usually healthy and need no treatment

They may have very mild anaemia and small red cells, usually without symptoms (MedlinePlus Genetics).

SOLIDThe severe form shows between 6 and 24 months of age

Pallor, poor growth, mild jaundice, enlarged liver and spleen (GeneReviews, Langer 2024).

SOLIDLifelong transfusions overload the body with iron

Each transfusion adds iron the body cannot get rid of, so patients need iron chelation (GeneReviews).

SOLIDCyprus cut affected births to fewer than 5 a year

Against 70–80 expected (Telfer et al. 2006). A 2013 review gives an expected 30–50; either way the drop is very large.

SOLIDGene therapy freed most trial participants from transfusions

89% of 41 people on Zynteglo; 91% of 35 people on Casgevy with enough follow-up (FDA, via BioSpace and MLO). Single-arm trials, no decades-long data yet.

CAUTION"Vietnam has 13 million (or 14 million) carriers"

Newspapers round differently by year: 12, 13 or 14 million. The peer-reviewed figure is 13.8% of the population from the 2017 national survey (Bach et al. 2022).

CAUTION"Sardinia went from 1 in 250 to 1 in 4,000 births"

The 15-year review (about 1990) gives 1 in 1,000. The 1 in 4,000 figure is for 1996, cited in a Haematologica article; the original was not read.

CAUTION"Thalassemia genes protect against malaria"

This is Haldane's 1949 hypothesis, supported by many studies: a 2012 meta-analysis found people with two copies of mild alpha-thalassemia had about 37% lower odds of severe malaria (OR 0.63). The effect is much smaller than for the sickle gene, and the mechanism is unclear (Taylor et al. 2012, Lancet Infectious Diseases).

CAUTION"In Cyprus, carriers are banned from marrying"

Since 1983 the church has asked for a certificate of testing, not a "clean" result. Results stay confidential and couples may still marry (Cyprus Mail 2023; EJHG 2010 review table; secondary source).

WRONG"Thalassemia is contagious"

It is inherited, present in the genes from conception. It does not spread by contact, food or marriage (GeneReviews; MedlinePlus).

WRONG"Anaemia? Just take more iron"

Carriers have small red cells and are easily mistaken for iron deficiency; patients are usually iron-overloaded from transfusions. Small red cells alone cannot tell the two apart; iron studies and haemoglobin tests ordered by a doctor can (thalassemia diagnosis reference, thebloodproject.com; GeneReviews).

WRONG"Carrying the gene means being ill, and two carriers should not marry"

Carrying is not having the disease. Carrier couples can get genetic counselling and prenatal diagnosis, as Cyprus and Sardinia did (GeneReviews; Angastiniotis and Hadjiminas 1981).

Source: as given in each row; full list in Part 9.

Part 5

Where things stand

From transfusions and iron chelation to gene therapy. Each milestone has a year and a source.

Foundation · Transfusion and chelationStill the standard care for the severe form, letting children grow and develop normally. A stem cell transplant from a matched donor can cure, but not everyone has a donor.
Nov 2019 · A drug to reduce transfusionsFDA approves luspatercept. In a trial of 336 people, 21.4% cut their transfusion need by at least a third, against 4.5% on placebo.
Aug 2022 · First gene therapyFDA approves Zynteglo: the patient's own stem cells receive a working beta gene and are infused back. 89% of 41 people no longer needed transfusions.
Nov 2023 and Jan 2024 · CRISPR editingThe UK approves Casgevy first (16 Nov 2023), then the FDA (16 Jan 2024). It does not fix the beta gene; it "switches back on" fetal haemoglobin. 91% of 35 people with enough follow-up went at least 12 months in a row without a transfusion.
Dec 2025 · A pillFDA approves mitapivat for anaemia in adults with alpha- or beta-thalassemia; liver tests are required because of cases of liver injury.
Vietnam · Transplants at homeSome hospitals now perform stem cell transplants for children with thalassemia, for example Hue Central Hospital since September 2024, with 16 cases in 18 months.

Source: GeneReviews (Langer 2024) (transfusion, chelation, transplant); FDA, 8 Nov 2019, luspatercept, BELIEVE trial (via ESMO, ASCO Post); FDA, Aug 2022, Zynteglo (via MLO, BioSpace); MHRA 16 Nov 2023 and FDA 16 Jan 2024, Casgevy (via Press Herald, BioSpace); FDA 23 Dec 2025, mitapivat (via HCPLive, secondary source); Đại biểu Nhân dân newspaper 2025 on Hue Central Hospital (secondary source). Drug names are for reference only, not treatment advice.

The price of gene therapy

In the US, Casgevy is priced at about 2.2 million dollars and Zynteglo at about 2.8 million for one treatment (press, secondary source). Patients need high-dose chemotherapy to "make room" in the marrow before receiving the edited cells, and only large centres can do it.

So for most patients in the world, safe transfusions and regular chelation still decide their quality of life.

Part 6

Verdict

Scores are Mark's assessment based on the sources in Part 9, not data from a study.

Understanding of the gene
5/5
Evidence that screening works
5/5
Treatment for people living with it
3/5
Access to new therapies in Vietnam
2/5
Strengths
  • Clear genetics; carrier tests are cheap and available
  • Two programmes over 40 years with measured results
  • Gene therapy has worked in trials
Weaknesses
  • Most Vietnamese figures come via the press
  • Gene therapy costs millions and needs high-dose chemotherapy
  • Screening touches marriage and childbearing, a risk of stigma

Label: SOLID. A disease "rare" in one place is a matter for millions of families in another, and the best prevention starts with a blood test.

More: why is screening a sensitive matter?

The Cyprus programme succeeded partly because the church and community stood behind it, but it also raised a question: how voluntary is it when a wedding needs a certificate? Programmes today stress counselling and the couple's own choice, and keep results confidential.

For people living with the disease, "prevention" must never turn into "should not have been born". They need good treatment, and many study, work and start families.

The "More" box is Mark's commentary, based on sourced facts in Parts 2 to 5 (Cyprus Mail 2023; EJHG 2010 review table).

Part 7

Lessons: read your blood count and know what to ask

You do not need to be a doctor. You need two lines of numbers and a few questions.

For reading and understanding, not a substitute for medical advice. The cut-offs below are screening signals used in studies, not for self-diagnosis.

Four steps: look at the MCV and MCH lines on a blood count; if low, ask the doctor whether iron tests and haemoglobin tests are needed; if you carry the gene, both partners get tested; if both carry it, ask about genetic counselling and prenatal diagnosis. 1 · look at MCV, MCHare red cells small?common cut-offs: 80 fL, 27 pg 2 · do not jumplow iron or carrier?ask about iron and Hb tests 3 · both partnersboth get testedideally before pregnancy 4 · if both carry itgenetic counsellingask about prenatal diagnosis "Carrier" is information to prepare with, not a sentence. Vietnam's prenatal screening guidance includes thalassemia (Decision 1807/QĐ-BYT, 2020)
The steps are habits of understanding suggested by Mark, not a clinical protocol. MCV 80 fL and MCH 27 pg are cut-offs used in many screening studies; among 300 pregnant women in Đồng Hỷ (Thái Nguyên), MCH 27 pg screened almost perfectly, while MCV missed some mild carrier types.Source: Lê Hoàng Xuân Mai et al. (2024), Đồng Hỷ study, Thái Nguyên (vnras.com); study of discrimination indices (PMC7573080); Decision 1807/QĐ-BYT (2020) and Decision 1999/QĐ-TTg (7 Dec 2020) on prenatal and newborn screening.
Keep your blood countTake a photo, note the year. If MCV and MCH stay low for years despite iron, that is worth asking about.
Test both partnersIf only one carries it, children will not have the severe form. Only when both carry it is there more to discuss.
Ask the right question"Could this result mean I carry thalassemia?", "Do I need a haemoglobin electrophoresis?"
Say "carrier", not "ill"Carriers are usually healthy. The right word reduces fear and stigma.
Self-check: five questions to take to a premarital check-up
  1. What are my MCV and MCH, and are they low?
  2. If low, should I have iron tests, haemoglobin electrophoresis, or a gene test?
  3. If I am a carrier, should my partner have the same test?
  4. If we both carry it, where can we get genetic counselling?
  5. If we have a pregnancy, when and where is prenatal diagnosis done?

The question list is Mark's suggestion, based on GeneReviews (genetic counselling, prenatal diagnosis) and Vietnam's Ministry of Health prenatal screening guidance (Decision 1807/QĐ-BYT, 2020).

Part 8

Read next

GeneReviews, "Beta-Thalassemia" (Langer, updated 2024)Full medical overview of diagnosis, treatment and genetic counselling.
Modell and Darlison (2008), Bulletin of the World Health OrganizationA global map of haemoglobin disorders, the basis for WHO programmes.
Genes and Rare Diseases #4: A drop of blood from the heelPKU and newborn screening: a small test that changes a whole life. Read
Genes and Rare Diseases #6: Sickle cellThe same HBB gene, a different fault, and a story about malaria. Read
Part 9

Sources

Main sources are original papers, the WHO Bulletin, GeneReviews and drug regulator decisions. This environment blocks PubMed, NIH, FDA and many Vietnamese news sites, so figures were checked against excerpts in search results (16 Oct 2026), without opening full texts. Secondary sources are marked.

  1. Modell B, Darlison M (2008), "Global epidemiology of haemoglobin disorders and derived service indicators", Bulletin of the World Health Organization 86(6): 480–487. SciELO
  2. Langer AL, "Beta-Thalassemia", GeneReviews, NCBI Bookshelf, posted 2000, updated 8 Feb 2024. NBK1426
  3. MedlinePlus Genetics, "Beta thalassemia". medlineplus.gov
  4. Bach KQ et al. (2022), "Thalassemia in Viet Nam", Hemoglobin 46(1): 62–65 (PMID 35950578). Read via abstract.
  5. Angastiniotis MA, Hadjiminas MG (1981), "Prevention of thalassaemia in Cyprus", The Lancet 1(8216): 369–371.
  6. Telfer P et al. (2006), paper on thalassaemia outcomes and prevention in Cyprus, Haematologica. haematologica.org
  7. Cao A et al. (1978), survey of beta-thalassaemia carriers in Sardinia, Journal of Medical Genetics 15(6): 443. jmg.bmj.com; 15-year review by Rosatelli et al. (Cagliari, about 1990); Haematologica article on the 1/4,000 rate in 1996. haematologica.org
  8. Table of carrier screening programmes in Europe, European Journal of Human Genetics 2010. PMC
  9. Taylor SM, Parobek CM, Fairhurst RM (2012), "Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis", Lancet Infectious Diseases 12(6): 457–468. PMC
  10. FDA: luspatercept (8 Nov 2019), Zynteglo (Aug 2022), Casgevy for beta-thalassemia (16 Jan 2024), mitapivat (23 Dec 2025); MHRA (UK): Casgevy (16 Nov 2023). Via ESMO, ASCO Post, MLO, BioSpace, Press Herald, HCPLive.
  11. Vietnam Ministry of Health, Decision 1807/QĐ-BYT (2020), technical guidance on prenatal and newborn screening and diagnosis; Prime Minister, Decision 1999/QĐ-TTg (7 Dec 2020). Via provincial documents.
  12. Lê Hoàng Xuân Mai et al. (2024), MCV and MCH for carrier screening in ethnic-minority pregnant women, Đồng Hỷ, Thái Nguyên. vnras.com
  13. Secondary sources: whonamedit.com, thebloodproject.com (Cooley 1925, naming, differential diagnosis); Cyprus Mail, 17 Mar 2023 (1983 certificate); Thanh Tra, VOV, Văn hoá, Lào Cai, PLO citing the National Institute of Hematology and Blood Transfusion (8,000 births a year, 2,000 severe, rates by ethnic group); Daily Upside, Press Herald (prices); Đại biểu Nhân dân (Hue Central Hospital).