1. By
Prof. Dr. Asmaa AbdulAziz

2. :Definition
The haemoglobinopathies are inherited disorders of
haemoglobinsynthesis )thalassaemias( orstructure )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.

5. Individuals with Haemoglobinopathy are:
either healthy carriers )trait ( i.e. unaware of their
carrier status unless specifically screened. If a couple
both carry a haemoglobinopathy trait there is a 1 in 4
chance with each pregnancy that their child will inherit
a clinically manifested haemoglobinopathy.
or having clinically manifested haemoglobinopathy

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

14. In children, sickle-shaped red blood cells often become
trapped in the spleen, leading to a serious risk of death
before the age of seven years from a sudden profound
anaemia associated with rapid splenic enlargement or
because lack of splenic function permits an infection.
Affected children may present with painful swelling of the
hands and/or feet )hand-foot syndrome(.
Survivors may suffer recurrent & severe painful crises, as
well as “acute chest syndrome” (pneumonia or pulmonary
infarction), bone or joint necrosis, or renal failure.

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

17. The sickle cell trait confers a selective advantage: resistance
to severe malaria. The mechanism of this protection however,
remains incompletely understood. Proposed mechanisms
include
decreased parasite growth in the red cells and
enhanced removal of parasitized cells by the spleen.
In patients with sickle cell trait, although some protection
against malaria and its complications is present, severe or
complicated malaria can occur.
However , severe hemolytic & infarctive crises are anticipated
if patients with sickle cell diseases get 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

26. In Bahrain Genetic disorders of haemoglobin are prevalent.
In a study of the hospital population covering
Bahrainis, it was found that 198, 56
•Sickle-cell disease was 2% of newborns
•Sickle-cell trait was 18% of newborns
•Carriers of the thalassaemia gene was 24% of newborns .
From this study it was concluded that
•The mild form of SCD predominates.
•Hematological values are similar to those of patients from
Eastern Province, Saudi Arabia, where the mild form of the
disease predominates

27. Sickle-cell disease in Bahrain and Saudi Arabia presents
special features. SCD in this area is clinically mild, and
. mortality is low in both children and adults
However, some cases died from septicemias &
.Pneumococcal diseases
In this study the most precipitating factors for crisis
:were
 Exposure to cold )45% of cases(.
 Fever or elevated body temperature )35%(,
 Exhaustion & severe physical activity )35%(,
 Hot humid weather )10%(
 Crowded places )10%(

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.

29. The control program depends on the characteristics & the
requirements of individuals with haemoglobinopathies.
Sickle cell disorders: :People with sickle cell disorders
• can have attacks of very severe pain
• can get serious, life-threatening infections
• are usually anaemic
• need medicines )antibiotics & Pneumococcal vaccine(
throughout their lives to prevent infections.
Thalassaemia major: People with thalassaemia major
• are very anaemic
• need blood transfusions every four to six weeks,
• need injections and medicines throughout their lives.
There are also other, less common, haemoglobin
disorders. Many of these are not serious.

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(

31. The antenatal screening programme
Parent screening for sickle cell and thalassaemia aims to
• identify women/couples at risk of a pregnancy with sickle cell or
thalassaemia disorders and
• provide appropriate referral & care for prenatal diagnosis with
continuation or termination of pregnancy according to women’s
choices.
In most of the countries where sickle-cell disease is a major
:public health concern
•National programmes for its control do not exist.
•Basic facilities to manage patients are absent,
•Screening for sickle-cell disease is not common practice
The diagnosis of the disease is made when severe
complication occurs.
As a result, more than 50% of the children with the severe
form of the disease die before the age of five from infection
or severe anaemia

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

34. NEONATAL SCREENING
The newborn sickle cell screening is part of the existing
bloodspot programme for Phenylketonurea )PKU( and
congenital hypothyroidism )CHT(.
Neonatal haemoglobinopathy screening primarily aims to
identify infants with SCDs , in order to start prophylactic
antibiotic therapy and vaccination ) Pneumococcal
vaccine( as early as possible.
detects carriers. For each baby detected with SCDs,
neonatal screening detects between 17 and 100 sickle cell
carrier babies. Parents of a carrier child should be
informed about the carrier result

35. In UAE, a standard form for neonatal screening is issued to every baby
born hospital, where 99% of deliveries occur, and mothers are informed
.about the procedures &importance of neonatal screening
.in January 1995 by screening for Phenylketonurea
in January 1998. Screening for congenital hypothyroidism
In January 2002, the Ministry of Health decided to launch a pilot
study for neonatal screening of sickle cell disease before expanding it
.at the national level
Newborn infants are brought to MCH centre on the fifth day for collection
of blood samples by heel prick onto filter paper
The aim of the Screening program for haemoglobinopathy is to:
•To detect infants with haemoglobin traits,
•To identify children with clinical disease and
•To counsel couples at risk for having future baby with sickle cell
disorders.
All infants confirmed with sickle cell disease started prophylactic
penicillin by the age of 2 months and follow-up was arranged with the
.cooperation of haematologist

36. Genetic counseling
It is the process through which knowledge about the genetic
aspects of illnesses is shared by trained professionals with
those who are at an increased risk or either having a genetic
disorders or having them to be passed to their unborn
offspring.
Genetic counseling is aiming to
•replace misunderstandings of the causes of genetic
disease with correct information
• informing parents about the resources available for
diagnosis, treatment and prevention.
•helping the families in decision making, which have life
long consequences
The family physician usually handles most of the genetic
counseling during routine clinical visits

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.

38. Pneumococcal diseases in children with Sickle cell
disorders :
•Children with sickle cell anaemia have an increased
susceptibility to severe bacteria infection, particularly from
Streptococcus pneumoniae. The risk of infection is greater in
the first 3 years of life specially at4 months.
•The incidence of Pneumococcal diseases for children with
sickle cell disease is 18.4cases per 100 patients/year
compared with 0.02 to 0.06 patientss per 100 healthy children
/year
•This infection may be the first clinical manifestation of
disease and carries .
•The case fatality rate of Pneumococcal diseases in these
children is 30%

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

40. Pneumococcal diseases in sickle cell children
include
• Pneumonia & bronchitis
• Pneumococcal meningitis
• Septicemias
• Ear infections
• Peritonitis

41. The Risk Factors for Recurrent Pneumonia in Children
which include:
•Sickle-cell diseases
•Impaired immune system( HIV, cancer, leukemia )
•Viral respiratory Infections
•Gastroesophageal reflux disorder
•Inborn lung or heart defects
•Asthma

42. •The causative agents : Streptococcus pneumonia
• Children under 2 years old are at highest risk for serious
disease.
•The organisms spread from person to person through close
contact.
•Pneumococcal infections can be hard to treat because the
bacteria have become resistant to some of the drugs that have
been used to treat them. This makes prevention of
Pneumococcal infections is more important.

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
Pneumococcal polysaccharide vaccine )PPV( -1 contains
purified capsular polysaccharide from each of 23 serotypes
of Pneumococcal bacteria
Pneumococcal conjugate vaccine )PCV( contains-2 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

45. )Pneumococcal polysaccharide vaccine )PPV
 Adults develop a good antibody response to a single dose of
PPV by the third week following immunization.
 Not used in children < two years of age because of poor
antibody responses .
The overall efficacy in preventing Pneumococcal bacteraemia is
50 to 70%
Post-immunization antibody levels begin to wane after five years

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 2nd month
Second dose of 0.5ml, at 4th month
A third dose of 0.5ml at 6th month
The fourth dose of 0.5ml at 13th 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

47. In general the Pneumococcal vaccine should be
given to Children having
•heart condition
•chronic lung ,liver disease
•diabetes mellitus
•weakened immune system
• Children with damaged spleen or no spleen Or Sickle
cell anaemia & thalassaemias .
These children should be managed as follow:

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 thePCV 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

50. Adverse effects following PCV
•25% had local redness, tenderness, or swelling
• Up to about 1 out of 3 had a fever
• Some children become drowsy, or had anorexia
So far, no serious reactions have been associated with this
vaccine.