Thalassemia is Not A Gift for Your Precious Little Angel
What is Thalassemia?
Thalassemia is a genetic blood disorder that affects the production of hemoglobin, the protein in red blood cells that carries oxygen to the body’s tissues. People with Thalassemia produce less hemoglobin than normal, which leads to anemia (UK: anaemia) and a variety of symptoms, such as fatigue, weakness, and shortness of breath, and other health complications. There are two main types of Thalassemia – Alpha Thalassemia and Beta Thalassemia - depending on which part of the hemoglobin molecule is affected. Both types can range from mild to severe; with more severe forms requiring frequent blood transfusions and other treatments to manage hemoglobin levels and symptoms.
Who?
Thalassemia is an inherited condition; meaning that it is passed down from parents to their children through genes. Data reports that it is most common among people of Mediterranean, some African, and Asian descent (Middle Eastern, South Asia, China, Southeast Asia), but can also affect people of any ethnicity (1)
As a complex genetic condition, each case is unique. 1 in every 25 Malaysians is a Thalassemia genecarrier
If both parents are carriers of the Thalassemia gene, each natural pregnancy in such couples carries a 25% risk of inheriting two copies of the mutated gene and develop Thalassemia major.
Types of Thalassemia
Normal hemoglobin consists of 2 Alpha chains and 2 Beta chains. Four Alpha genes are required to make enough Alpha globin protein chains. Two Beta genes for enough Beta globin protein chains.
In Alpha Thalassemia, the number of missing copies of Alpha genes determine the severity (fewer hemoglobin molecules). Specifically, abnormal copies of HBA1 and HBA2 genes on chromosome 16.
One gene missing – Alpha Thalassemia “Silent Carrier” won’t have symptoms but may pass the missing
Two genes missing – Alpha Thalassemia Carrier/ Alpha Thalassemia Minor carries the trait and may have mild symptoms of anemia.
Three genes missing – Hemoglobin H Disease or H Thalassemia causes moderate to severe anemia.
Four genes missing – Alpha Thalassemia Major/ hydrops fetalis. Rarely does a baby inherit all 4 missing genes and dies before birth, or shortly after. In Hb Barts hydrops fetalis syndrome, the fetus is born with fluid accumulation in the body (generalized oedema), in the spaces of the abdomen
(ascites), that affects nearby organs, causing abdominal pain, and fluid collection on the lungs and surrounding the heart (pleural and pericardial effusions). (2)
In Beta Thalassemia, altered Beta globin genes on chromosome11 determine the severity.
One altered gene - Beta Thalassemia Minor/ Carrier of the altered gene experiences mild anemia.
Two altered genes – Beta Thalassemia Major causes serious anemia symptoms. Rarely depending on the functional level of the impaired HBB gene the anemia may be moderate to severe, and it is known as Beta Thalassemia Intermedia. The bone marrow expands, causing bones to widen, resulting in an abnormal bone structure (face and skull) that is also thin and brittle, thus prone to breakage.
What’s the Risk? Risk to Child?
Patients with Thalassemia minor can lead normal or near-normal lives with relatively mild anemia, and usually asymptomatic which needs no treatment under normal circumstances. Depending on the severity of the condition, the range of health problems include anemia, fatigue, growth delays, and other complications.
A baby will usually start presenting symptoms after the age of 6 months. Newborn babies (neonates) have fetal hemoglobin, which is later replaced by “adult” hemoglobin and if this does not happen due to Thalassemia gene, the symptoms begin.
The life expectancy of Thalassemia patients can vary widely depending on the type and severity of the condition, as well as access to medical care and treatment.
People with Thalassemia major, the most severe form of the condition, typically have a shortened life expectancy if not properly managed treatment. The condition causes severe anemia, and other complications that can lead to organ damage and failure if left untreated.
While Thalassemia is a lifelong condition, modern medicine has improved treatments to enable better and longer life.
Treatment Options
Patients with Thalassemia or Beta Thalassemia receive occasional blood transfusions, specifically when the body is stressed (infection, pregnancy, surgery).
Patients with Beta Thalassemia major, however get regular blood transfusions (every 3 – 4 weeks) from local blood banks which depend solely on voluntary blood donors (3). Each procedure can take one to four hours. Here, blood transfusion is necessary to maintain optimum red blood cells and healthy hemoglobin levels.
Iron chelation therapy removes excess iron from the body that occurs from frequent blood transfusions. Thalassemia minor, patients may have a normal life and may not require regular medical treatment. They may still experience mild fatigue, anemia, and jaundice symptoms.
Thalassemia major patients may live well into adulthood with the right but costly and usually life-long management. Patients on the lower socioeconomic level will not be able to afford this over long-term.
(4) Economic burden in the management of transfusion-dependent thalassaemia patients in Malaysia from a societal perspective
Few healthcare facilities worldwide are equipped to assist with severe Alpha Thalassemia Major. Fetal blood transfusion or Intrauterine Transfusion exists to help provide healthy red blood cells to a developing fetus experiencing anemia, a method more commonly used for blood Rh mismatch between mother and baby (5)
Should a baby survive because of fetal blood transfusions, chronic blood transfusions will be necessary until a stem cell transplant is possible.
A successful stem cell transplant is one promising treatment that may. Only hematopoietic stem cells can be used for such treatment and no other types of stem cells.
However, finding a suitable donor and other possible complications can impair this already long process. The global database of volunteer hematopoietic cells (6 World Marrow Donor Association (WMDA)) lists over 40 million stem cell donors, yet, finding a match is not possible for all patients. No organisation in Malaysia is listed in this global database, but Malaysia has its own national registry (7). The closer the match, the less chances of failure, such as the new cells attacking the patient’s cells, called Graft versus - Host Diseases (GVHD). This can happen 6 months after the transplant or up to 2 years later.
Cancer Research UK states that the closest match is among blood siblings, and even then, a 1 in 4 chance of a match. Yet, only 1 in 5 patients have a family member as a match.
Survival rates are reported as between 66%-99% for sibling matches, and 62%-100% for unrelated donor matches.
The transplant treatment includes high doses of chemotherapy. 30% of high-risk patients reject the stem cells.
https://www.sciencedirect.com/science/article/pii/S1658387617300602
Prevention & Testing
As it is caused by mutations in the genes, Thalassemia cannot be prevented entirely. However, there are ways to reduce the risk of having a child with these conditions. Genetics begins to play a role here.
For starters, awareness is required to know if one is a carrier of the mutated gene. Carrier genetic test is a useful tool for diagnosing the type and presence of Thalassemia and determining a person’s risk of passing on the mutated genes or the condition to their children.
Several types of genetic tests can be used to diagnose Thalassemia, including:
Carrier Genetic Test (CGT) is used to determine whether a person carries a mutation in one or both of the genes that cause Thalassemia. This can be done using a blood sample or other tissue sample. https://mycgxlab.com/cgt/
There is also a specific test offered for Thalassemia that involves analyzing a person’s DNA to identify specific genetic mutations associated with Thalassemia. This can be done using a blood sample, cheek swab, or other tissue sample.
Preimplantation Genetic Test (PGT) is a powerful test that screens embryos created through in vitro fertilization (IVF) for Thalassemia before they are implanted in the uterus. Only embryos that do not carry the Thalassemia gene are implanted. https://mycgxlab.com/pgt-m/
Prenatal testing is performed during pregnancy to determine whether a fetus has Thalassemia. Methods of prenatal testing include either chorionic villus sampling (CVS) and amniocentesis, (a small sample of the fluid that surrounds the foetus). Both are invasive procedures.
However, there is an easier method available known as the– Non-Invasive Prenatal Test (NIPT) that involves taking a small amount of blood (10mL) from the mother, and CGx can do it for you at as early as 9 weeks of gestation. The blood is then sent to the laboratory for genetic analysis.
ACOG recommends NIPT to be offered to all pregnant women, regardless of maternal age or risk factors3
3ACOG Practice Bulleting No. 226 (2020). Screening for Fetal Chromosomal Abnormalities.(8)
4Gregg AR, et al (2016). Noninvasive prenatal screening for Fetal Aneuploidy.(9)
As a prevention option, the carriers of the Thalassemia gene may choose to avoid having children altogether, or to adopt or use donor eggs or sperm to reduce the risk of passing on the condition.
In cases where prenatal DNA testing reveals that a fetus has Thalassemia, there are several options available to parents. These can include:
Continue the pregnancy and prepare for a child with Thalassemia, depending on the severity of the condition. This can involve planning for medical care and treatment, such as regular blood transfusions, iron chelation therapy, and other interventions.
Termination of the pregnancy: In some cases, parents may choose to terminate the pregnancy if they do not feel prepared to care for a child with Thalassemia Major or if the health risks to the fetus are severe. However, this is subject to the medical ethics guidelines and the regulations under the Ministry of Health of the expecting mothers’ respective countries.
Adoption or use of donor eggs or sperm: Parents who are carriers of the Thalassemia gene may choose to adopt a child or use donor eggs or sperm to avoid passing on the mutated gene. Again, this is subject to the regulations of the Ministry of Health in the respective countries and also the medical ethics guidelines.
Ultimately, the decision regarding a fetus found to have Thalassemia is a personal one that should be made in consultation with medical professionals and genetic counsellors.
Early diagnosis is vital to begin necessary treatment to manage the condition and improve quality of life for those affected.
Genetic testing is an essential tool for diagnosing Thalassemia and identifying carriers of the mutated genes. By informing a person’s risk of developing Thalassemia or passing the condition on to their children, genetic testing can help individuals make informed decisions about family planning and medical care.
At CGx, we offer a range of genetic tests to screen for Thalassemia carriers and other genetic disorders. Our goal is to help individuals and families make informed decisions about their health and genetic risks, and to provide the information and support needed to manage genetic conditions.
PGT-A Preimplantation Genetic Testing for Aneuploidies – reproductive technology used with an in vitro fertilisation (IVF) cycle. It is used to analyse the chromosomes of the embryos before their transfer into the womb. It increases the chance of becoming pregnant, lowers the risk of miscarriage or risks of having a chromosomally abnormal child.
PGT-M Preimplantation Genetic Testing for Monogenic Diseases – enables couples with an inheritable genetic condition in their family to avoid passing it on to their children. It is a powerful test performed prior to implantation to help identify single gene defects within embryos created through IVF to avoid conceiving a child with a genetic disorder.
Carrier Genetic Test (CGT) – provides information to assist in preconception planning and prenatal diagnostic testing for couples identified as carriers of genetic disorders or diseases. CGx offers both Focus CGT covering 7 genes (including Alpha & Beta Thalassemia) & Expanded CGT covering 420 genes.
By raising awareness about Thalassemia and the importance of genetic testing, we hope to empower individuals and families to take control of their health and make informed decisions about their future with evidence-based molecular diagnostics (or genetic tests).
Thank you for taking the time to read this blog post, and please don’t hesitate to share this with your friends and family members, or to reach out to us with any questions or concerns about Thalassemia or genetic testing.
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