Haemoglobin (Hb) is a protein in the red blood cells that transports oxygen from the lungs to the rest of the body. It consists of two alpha and two beta globin chains.
Inherited conditions of haemoglobin are becoming an increasing health burden, with an estimated 7% of the world’s populations having the gene mutations responsible for these disorders.
These conditions are classified into haemoglobin variants and thalassaemia, both of which follow an autosomal recessive inheritance, i.e. two abnormal genes must be present for the disease or trait to develop.
The haemoglobin variants (haemoglobinopathies) have changes in the normal amino acid sequence of globin.
Haemoglobin E (HbE) is a variant that affects the production of adult haemoglobin (HbA) and is found in Malaysia. It occurs when there is a gene defect of one or both beta globin chains; the former is a carrier (heterozygous) and is healthy; the latter (homozygous) has no major problems apart from slight anaemia.
If both parents are HbE carriers, each of their children have a one in four chance that the faulty gene will not be inherited; a one in two chance that the faulty gene will be inherited from one parent to become a carrier; and a one in four chance that the faulty gene will be inherited from both parents, resulting in slight anaemia.
Haemoglobin S (HbS) is a variant of HbA in which there is an amino acid substitution in the beta globin chain.
The heterozygous almost always have no symptoms, but the homozygous suffer from sickle cell anaemia with its acute and chronic complications, including haemoly-tic crises.
It was initially found in Africa, the Middle East and parts of India, but is now found in Europe, the Americas and the Caribbean because of human migration.
Haemoglobin C (HbC) is another variant of HbA and is found in Malaysia. It occurs when there is a gene defect at the same position of HbS. The heterozygous have no symptoms, but the homozygous have slight anaemia.
Thalassaemia results from an underproduction of one or two of the globin chains, with alpha-tha-lassaemia and beta-thalassaemia occurring in gene defect(s) of the alpha and beta chains respectively.
Thalassaemia has to be distinguished from the haemoglobinopathies above.
A person who has the thalassaemia gene, but not the condition is called a “carrier” (heterozygous), or alternatively, is described as having the thalassaemia trait.
If both parents have the beta thalassaemia trait, each of their children has a one in four chance that the faulty gene will not be inherited; a one in two chance that the faulty gene will be inherited from one parent to become a carrier; and one in four chance that the faulty gene will be inherited from both parents, resulting in thalassaemia.
The beta thalassaemia trait is found in 3% to 5% of Malays, Chinese and Orang Asli in Malaysia, and is rare in Indians. It is also found in people of Mediterranean and Middle Eastern origin.
The inheritance of alpha thalassaemia is more complex because four potentially faulty genes are involved, and not just two.
The children of parents who have the alpha thalassaemia trait would have alpha thalassaemia if they have three or four copies of the faulty genes. If they have one or two copies of the faulty gene, they will be carriers.
The amount of Hb produced in thalassaemia major is limited (or even absent), resulting in severe anaemia which is treated with blood transfusion.
Repeated blood transfusions, ineffective red blood cell production and increased intestinal absorption lead to iron overload in beta-thalassaemia major persons who need medicines to prevent it and early death.
Homozygous alpha thalassaemia major persons do not survive birth.
Heterozygous beta or alpha thalassaemia persons and those with the trait lead a normal life.
Haemoglobins E & C and thalassaemia
Complications may arise when a person with HbE has a child with a person with beta thalassaemia.
Each of their children has a one in four chance that the faulty genes will not be inherited; a one in four chance that the faulty HbE gene will be inherited from one parent to become a carrier; a one in four chance that the faulty beta thalassaemia gene will be inherited from one parent to become a carrier; and a one in four chance that both the faulty HbE and thalassaemia genes will be inherited from each parent and a child be born with severe disease requiring life-long treatment, including blood transfusions.
When a person with HbC has a child with a person with beta thalassaemia, the children may be similarly affected.
Diagnosis of the haemoglobinopathies and thalassaemia can be made by a blood test. As the condition is inherited, only one test is needed in a person’s lifetime.
It is advisable for persons with HbE not to have children with someone with beta-thalassaemia. However, HbE persons can have children with someone with alpha-thalassaemia or HbE.
The prevention of homozygous beta thalassaemia major requires persons with beta thalassaemia trait avoiding having children with someone else with the beta thalassaemia trait as they have a one in four chance of having a transfusion-dependent beta thalassaemia major child.
However, the person with beta thalassaemia trait can have children with someone with an alpha thalassaemia trait.
Screening can be done when planning for a family or during early pregnancy. If the result reveals that the person has a haemoglobinopathy or thalassaemia trait, the spouse or partner and other family members will be offered the same test.
If pregnant, the screening should ideally be done before 10 weeks’ gestation so that further tests, i.e. chorionic villi sampling (CVS) or amniocentesis can be done to determine if the foetus has thalassaemia or HbE/thalassaemia.
There is a risk of miscarriage with both these tests, with CVS having a lower risk.
If the test reveals that the foetus has thalassaemia major or HbE/thalassaemia, advice about the continuation of the pregnancy will be provided.
Counselling is essential to prevent an increase in the incidence of haemoglobin variants and the thalassaemias.
It is important to remember that a single blood test once in your life is all that is necessary to identify a haemoglobinopathy and thalassaemia.
Dr Milton Lum is a past president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association.
The views expressed do not represent that of any organisation the writer is associated with. The information provided is for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.