Category: MEDICINE

Importance of premarital screening in the prevention of thalassemia in Pakistan.

With over 100,000 active patients and 5000 affected babies being born every year, thalassemia remains a common genetically inherited blood disorder in Pakistan.

The diagnosis of thalassemia is pretty simple. A Complete Blood Count (CBC), measuring the concentration of haemoglobin, size and number of Red Blood Cells is performed as an initial test, followed by Haemoglobin electrophoresis to confirm the diagnosis of this disorder. Unfortunately, the management process, including regular blood transfusions, iron chelation therapy, and consistent consultations with a haematologist, is expensive and most children do not receive the care they require.

What is premarital thalassemia screening?

Premarital thalassemia screening refers to the process of determining the presence of thalassemia carrier genes in both partners before they get married.

If both spouses are carriers, there is a considerable likelihood of the transfer of mutated genes to their offspring. Approximately, there is 25% chance of their offspring being thalassemia major, 50% chance of them being thalassemia minor (carriers of the disorder), and only 25% probability being normal.

The presence of a carrier gene in only one of the partners is considered safe as it produces progeny with a 50% chance of normal genes, and 50% of carrier genes. No thalassemia major child is born to such a couple.

Premarital screening reduces the rate of genetic disorders as prevalent as thalassemia.

The technique is seen to be 100% efficient in Cyprus where no child with thalassemia was born from 2002 to 2007 followed by a massive premarital screening

img3

Why is premarital thalassemia screening important?

1. Helps identify asymptomatic carriers

Since it is a recessive gene disorder, thalassemia carriers are asymptomatic. In recessive gene disorders, both parents contain one mutated gene and the other normal one. One mutated gene coding for the disease is inherited by each parent.

This means that thalassemia carriers aren’t aware of the potential hazards that can happen if they mate with another carrier. Both carriers, asymptomatic, together have a considerably high probability of having children suffering from thalassemia.

2. Antenatal screening is sophisticated

Some parents choose to screen their genetics after a baby is conceived. Antenatal screening of thalassemia takes place within 19 weeks of pregnancy, through a blood test.

A positive result indicating that the mother is a thalassemia carrier is followed by paternal screening. In most cases when both parents are carriers, a further diagnostic test is suggested to confirm the presence of disease in the fetus.

1% of all diagnostic tests result in miscarriage. If the tests indicate that the fetus has thalassemia, an abortion is suggested.

Since the antenatal screening of thalassemia is sophisticated, and abortion is considered unethical by many, it is better to screen for thalassemia before marriage. It is much easier and more cost-effective compared to antenatal screening

3. Consanguineous marriages are common

Pakistan has one of the highest rates of cousin marriages in the world. With 49.6% of all women marrying their first cousins and 8.3% to their second cousins, the risk of birth defects in children is doubled.

Both parents share the same family history in consanguineous marriages, so the probability of recessive genes expressed in offspring increases. According to a 2004 study, 40.6% of beta-thalassemia cases are the outcome of cousin marriages.

In such circumstances, the need for premarital screening can not be stressed enough. The high prevalence of thalassemia in Pakistan can only be mitigated if potential spouses are screened for the disease, and provided genetic counseling if found to be carriers.

A mass awareness campaign and a subsequent screening premarital screening program can save Pakistan from such alarmingly high statistics of thalassemia patients.

The Need of Iron Chelation Therapy for Thalassemia Patients.

Iron chelation is a medical procedure used for the treatment of iron overload caused by excessive transfusions, or from birth1. Iron chelation therapy has been found to improve some symptoms of thalassemia.

Iron Chelation Therapy

This can be achieved by administering a chemical substance which binds to the iron and removes it from the body. Symptoms like fatigue, anemia and growth failure show improvement after administration/initiation of Iron chelation therapy. The most common form of chelation therapy is deferoxamine (DFO; a synthetic dimer of 2-picolinic acid). DFO works by binding to ferric ions (Fe3+), which are usually bound to transferrin and other proteins in blood plasma or stored in tissues like liver cells. The following paper will further discuss the use of Iron Chelation as a treatment method for thalassemia patients.

Necessity of Iron Chelation Therapy

Iron chelation therapy is a crucial part of management for those with thalassemia having excessive iron accumulation due to increased breakdown of red blood cells and frequent blood transfusions. It has been available since the 1960s, when it was first used to treat patients with thalassemia major and later those with thalassemia minor.

img2

Causes of Iron Overload

Iron overload, whether hereditary or acquired, can be caused by a variety of factors, including frequent transfusions, iron usage (typically as a supplement), and chronic hepatitis. Hereditary hemochromatosis (all types), African iron overload, sickle cell disease, major beta-thalassemia, sideroblastic anemia, enzyme deficiency (pyruvate kinase, G6PD), and rare transport protein disorders (Atransferrinemia, Aceruloplasminemia) are among the genetic disorders that cause iron overload2. The patient’s small intestine absorbs a lot of iron, which builds up in the liver, pancreas, and some regions of the brain, impairing important activities.  Due to the generation of free radicals as a result of iron overload, significant complications such as mental retardation and early neurological illnesses (Alzheimer’s, multiple sclerosis, Huntington’s disease) might occur. 71% mortality in cardiac disease due to iron accumulation in myocardium is a significant complication of iron overload in beta-thalassemia. In order to avoid such serious complications, it is essential to suppress LPI (Labile Plasma Iron) and remove excess iron. Thus, the best selection for treatment of iron overload is iron chelation therapy.

Administration of Iron Chelation Therapy

Each transfusion unit includes approximately 250 milligrams of iron2. The body can only excrete a small quantity of iron per day, roughly one milligram, which is sloughed off in the skin via sweat. As a result, extra iron becomes trapped in important organ tissues such as the anterior pituitary, heart, liver, pancreas, and joints. When iron levels reach dangerous levels, disorders like diabetes, cirrhosis, osteoarthritis, heart attack, and hormone imbalances can occur. Hormone abnormalities can cause hypothyroidism, hypogonadism, infertility, impotence, and sterility. Chronic weariness, mood changes, and memory loss are all possible signs. Excess iron, if not handled, can lead to organ failure and death. In general, significant iron loading of the liver can be detected after about six months of monthly transfusions, while cardiac loading takes about eight to ten years3. Iron accumulation in liver is proportional to the duration of iron overload. In contrast, iron deposition on heart has a delayed but abrupt onset.

Advantages of Iron Chelation Therapy

Chelation treatment attempts to balance the rate of iron build up from blood transfusions by boosting iron excretion in urine and/or faeces using chelators4 . If chelation is delayed or insufficient, it will be essential to eliminate iron at a rate greater than this. Excess removal of iron can also damage the tissues therefore it is important to be cautious about the patient’s iron levels before starting chelation. To avoid toxicity from over-chelation, iron chelation therapy in patients is usually recommended at a serum.

References

  1. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476479/
  2.  Iron Reduction: Chelation Therapy https://irondisorders.org/chelation-therapy/
  3. Treating Thalassemia: Chelation  https://www.thalassemia.com/treatment-chelation.aspx
  4.  IRON OVERLOAD AND CHELATION – Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) https://www.ncbi.nlm.nih.gov/books/NBK269373/