1. By Prof. Dr. Asmaa AbdulAziz

2. Definition: The haemoglobinopathies are inherited disorders of haemoglobin synthesis (thalassaemias) or structure (sickle cell disorders) that are responsible for significant morbidity and mortality allover the world. They are seen mainly in individuals who originate from Africa, the Middle East,, the Mediterranean, Asia and the Far East. However, the increased mobility of the world’s population and inter-ethnic mixing lead to prevailing of these conditions within any region of the world.

3. These disorders result in errors in oxygen-carrying capacity of haemoglobin . Diseases linked to genetic predisposition are not only kill prematurely, but result in long years of ill health and disability, loss of work and income, possible poverty, loneliness and depression .

4. Sickle cell and thalassaemia are inherited disorders that are passed on from parents to children through unusual haemoglobin genes. People only have these disorders if they inherit two unusual haemoglobin genes – one from their mother, and one from their father. People who inherit just one unusual gene are known as ‘carriers’. (Some people call this having a ‘trait’.) Carriers are healthy and do not have the disorders.

6. Who can be a carrier? Anyone can be a healthy carrier. This means you are more likely to be a carrier if your ancestors came from the Mediterranean (for example Cyprus, Italy, Portugal, Spain), Africa, the Middle East, India, Pakistan, South America or south and south-east Asia. Is it important to know if you are a carrier? 1- Healthy sickle cell carry may have some problems in rare situations (Lack of oxygen ,for example), when having an anesthetic or during deep-sea diving. Knowing that you carry sickle cell can help you manage these situations. However, people who carry thalassaemia or other unusual haemoglobin genes do not experience these problems. 2-If a carrier gets married from another carrier (Consanguinity) they will have one in four baby with clinically manifested disorders

7. The diagram below shows the chances (for each pregnancy) of two carrier parents having a child with a sickle cell or thalassaemia disorder.

8. If the mother is anemic & the father is healthy carrier 50% of the off springs are carriers and 50% is anaemic

9. Sickle Cell is a condition that affects the normal oxygen carrying capacity of red blood cells. When the cells are de-oxygenated and under stress in sickle cell conditions, they can change from round flexible disc-like cells to elongated sickle or crescent moon shape. The effect of these changes is that the cells do not pass freely through small capillaries and form clusters, which block the blood vessels. This blockage prevents oxygenation of the tissues in the affected areas resulting in tissue hypoxia and consequent pain (known as sickle cell crisis pain ) other symptoms of sickle cell disorders include severe anaemia, susceptibility to infections and damage to major organs.

10. The term sickle-cell disease is preferred because it is more comprehensive than sickle-cell anaemia.

13. 2-The clinically significant haemoglobinopathies are listed in following Table

15. Thalassaemia Major : It is the most severe form of thalassaemia, results in the inability of the body to produce haemoglobin, resulting in life threatening anaemia. Those with the condition require regular therapeutic treatment and blood transfusion . Bone marrow transplantation is a treatment option

16. The impacts of genetic disorders on infectious diseases (Malaria & Sickle cell disorders) Many studies showed reduced morbidity and mortality from malaria ( Falciparum ) patients with thalassemia major and minor (the carriers) (up to 50%), and decreased numbers of circulating parasites (by 80%) The mechanism of resistance may consist of decreased parasite replication within the erythrocyte or enhanced splenic clearance of parasitized erythrocytes . A person who carries the sickle cell gene has a survival advantage against malaria

18. Prevalence of haemoglobinopathies The World Health Organization (WHO) estimates that globally at least : approximately 5% of adults are carriers for a haemoglobin condition 2.9% for thalassaemia and 2.3% for sickle cell diseases Carriers are found allover the word because as a result of migration the populations of different ethnic groups to different regions of the world.

20. Prevalence of Sickle cell disorders

22. SITUATION in Africa The highest prevalence of sickle-cell trait is in parts of Africa & among people with origins in equatorial Africa, the Mediterranean basin and Saudi Arabia. In Africa, the highest prevalence of sickle-cell trait occurs between latitudes 15° North and 20° South

23. Over 300 000 children are born each year with a severe haemoglobinopathy. 30% are born with thalassaemia syndromes while 70% have sickle-cell anaemia With worldwide migration, these diseases are as much a feature of Europe, the United States and Australia as of the countries where they originated. Prevalence varies from under 0.1 births per 1,000 in some parts of the world to more than 20 per 1,000 in parts of Africa . In America, approximately 70,000- 80,000 people suffer from sickle cell disease . They are mainly of African Origin

25. The situation in KSA: In a study carried in KSA ,the incidence of hemoglobulin S for the studied neonates was 14.4% and ranged from 0.8% in Najran to 26.4% in Al-Qurayyat, KSA. In the eastern provinces the disease is generally milder whereas in the western provinces the disease is severe and similar to that reported in African populations

28. National Control program for haemoglobinopathies: The development of appropriate national control programme is now accepted and introduced in many parts of Asia such as in Bahrain, the Islamic Republic of Iran and Saudi Arabia . China, India, Indonesia, Malaysia, Maldives, Singapore and Thailand.

30. National Control program for sickle cell diseases 1- setting up sickle-cell screening and genetic counseling programmes in high prevalence countries. The disease should be identified during the prenatal period or at birth as part of a routine screening programme. Genetic counseling and screening can lead to reduction in the number of children born with the trait. The programme should be developed at the primary care level with appropriate referral system. 3-Parents must be counseled to seek medical care for all febrile events in children with sickle cell diseases. 2-Supplementation of antibiotics, rest, good nutrition, folic acid 3-Training of health personnel in prevention, diagnosis and case management should be an integral part of the national programme. 4-Integration of national control program for sickle-cell disease within the national programmes for prevention & control of non-communicable diseases (Cancer , Diabetes)

32. ANTENATAL SCREENING Pregnancy Offer screening Blood sent to laboratory for haemoglobinopathy Screen Positive results Information & counseling-Offer partner screening Partner screening Blood sent to laboratory for haemoglobinopathy Screen Positive results: At risk couple Information & counseling-Offer prenatal diagnosis Affected fetus- Information &counseling Parents Make- Informed Choice Termination of Pregnancy Prenatal diagnosis Fetal blood Sampling/ Chorionic Villus sampling Negative Result Information: No further action Unaffected Fetus Information- No further action Negative Result Information: No further action Continue with Pregnancy

33. Premarital diagnosis : In the Saudi society, consanguineous marriages are high (60%). Recently, the Saudi government introduced a new legislation regarding premarital testing for the 2 common genetic disorders; namely, sickle cell trait and thalassemia. The advantage of premarital diagnosis is that : affected births could be prevented if couples at risk were identified.

37. A survey of 500 parents, with children who have a genetic diseases was carried, to find their knowledge about genetic diseases indicated that the majorities were unaware of etiologies, symptoms, inheritance and therapies. This was particularly true for parents with lower education. Until recently a genetic counselor only advised of possibilities of recurrence of such a disease in the family. The new policy of genetic counseling is to help the family in making the correct decision for preventing the disease in the extended family and the prevention of a similar condition in future pregnancies .

39. Age distribution of pneumococcal bacteremia in children with sickle cell disease or HIV and healthy children at Boston Medical Center, 1981–1998 .9

43. Pneumococcal vaccine can help prevent serious Pneumococcal disease, such as pneumonia, bronchitis meningitis and septicemia & ear infections.

44. There are two types of Pneumococcal vaccine: 1- Pneumococcal polysaccharide vaccine (PPV) contains purified capsular polysaccharide from each of 23 serotypes of Pneumococcal bacteria 2-Pneumococcal conjugate vaccine (PCV) contains capsular polysaccharide from seven serotypes of Pneumococcal bacteria conjugated to protein The vaccines are inactivated, do not contain live organisms and cannot cause the diseases against which they protect.

46. Pneumococcal conjugate vaccine (PCV) The antibody response in young children can be improved by conjugating the polysaccharide to proteins. The conjugated vaccine is immunogenic in children . The efficacy is 97% after giving the fourth dose The vaccine protects against Pneumococcal meningitis, bacteraemia, pneumonia and otitis media. For children under one year of age: ) First dose of 0.5ml of PCV at 2 nd month Second dose of 0.5ml, at 4 th month A third dose of 0.5ml at 6 th month The fourth dose of 0.5ml at 13 th month Subcutaneous at anterolateral thigh Children over one year of age and under five years of age: A single dose of 0.5ml of PCV (subcutaneous upper arm)

48. Infants under one year of age: Give PCV vaccine as routinely recommended at two and four months of age with a booster dose at around 13 months of age. Children aged 12 months to < five years If they have a single dose of PCV before ,they should receive a second dose of PCV ( Separated by two months) because they may have a reduced immune response for the first dose of the vaccine. At-risk children aged five years and over PCV is not recommended .

49. Don’t give the PCV vaccine to Children had a serious (life-threatening) allergic reaction to a previous dose of this vaccine ( as it contains protein) Give the PCV vaccine to Children even with minor illnesses, such as mild fever or diarrhea Postponed the PCV vaccine for children who are moderately or severely ill .Wait until they recover before getting the vaccine

51. Best Wishes