:DefinitionThe haemoglobinopathies are inherited disorders ofhaemoglobinsynthesis )thalassaemias( orstructure )sicklecell disorders( that are responsible for significant morbidity.and mortality allover the worldThey are seen mainly in individuals who originate fromAfrica, the Middle East,, the Mediterranean, Asia and the FarEast. However, the increased mobility of the world‘spopulation and inter-ethnic mixing lead to prevailing of.these conditions within any region of the world
These disorders result in errors in oxygen-carryingcapacity of haemoglobin . Diseases linked to geneticpredisposition are not only kill prematurely, but resultin long years of ill health and disability, loss of workand income, possible poverty, loneliness anddepression.
Sickle cell and thalassaemia are inherited disorders that arepassed on from parents to children through unusualhaemoglobin genes.People only have these disorders if they inherit two unusualhaemoglobin genes – one from their mother, and one fromtheir father.People who inherit just one unusual gene are known as‘carriers‘. )Some people call this having a ‘trait‘.( Carriers arehealthy and do not have the disorders.
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
?Who can be a carrierAnyone can be a healthy carrier. This means you are morelikely to be a carrier if your ancestors came from theMediterranean )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 carrier1- Healthy sickle cell carry may have some problems in raresituations )Lack of oxygen ,for example(, when having ananesthetic or during deep-sea diving.Knowing that you carry sickle cell can help you managethese situations.However, people who carry thalassaemia or other unusualhaemoglobin genes do not experience these problems.2-If a carrier gets married from another carrier)Consanguinity( they will have one in four baby withclinically manifested disorders
The diagram below shows the chances )for each pregnancy( of two carrierparents having a child with a sickle cell or thalassaemia disorder.
If the mother is anemic & the father is healthy carrier 50% of the off springs are carriers and 50% is anaemic
Sickle Cell is a condition that affects the normal oxygencarrying capacity of red blood cells.When the cells are de-oxygenated and under stress in sickle cell conditions, theycan change from round flexible disc-like cells to elongatedsickle or crescent moon shape. The effect of these changesis that the cells do not pass freely through small capillariesand form clusters, which block the blood vessels. Thisblockage prevents oxygenation of the tissues in the affectedareas resulting in tissue hypoxia and consequent pain)known assickle cell crisis pain( other symptoms of sicklecell disorders include severe anaemia, susceptibility to.infections and damage to major organs
The term sickle-cell disease is preferred because it is morecomprehensive than sickle-cell anaemia.
The clinically significant haemoglobinopathies-2are listed in following Table
In children, sickle-shaped red blood cells often becometrapped in the spleen, leading to a serious risk of deathbefore the age of seven years from a sudden profoundanaemia associated with rapid splenic enlargement orbecause lack of splenic function permits an infection.Affected children may present with painful swelling of thehands and/or feet )hand-foot syndrome(.Survivors may suffer recurrent & severe painful crises, aswell as “acute chest syndrome” (pneumonia or pulmonaryinfarction), bone or joint necrosis, or renal failure.
Thalassaemia Major : It is the most severe form ofthalassaemia, results in the inability of the body to producehaemoglobin, resulting in life threatening anaemia.Those with the condition require regular therapeutictreatment and blood transfusion .Bone marrow transplantation is a treatment option
The impacts of genetic disorders on infectious diseases)Malaria & Sickle cell disorders(Many studies showed reduced morbidity and mortality frommalaria ) Falciparum( patients with thalassemia major andminor (the carriers) )up to 50%(, and decreased numbers ofcirculating parasites )by 80%( The mechanism of resistancemay consist of decreased parasite replication within theerythrocyte or enhanced splenic clearance of parasitizederythrocytes.A person who carries the sickle cell gene has a survivaladvantage against malaria
The sickle cell trait confers a selective advantage: resistanceto severe malaria. The mechanism of this protection however,remains incompletely understood. Proposed mechanismsinclude decreased parasite growth in the red cells and enhanced removal of parasitized cells by the spleen.In patients with sickle cell trait, although some protectionagainst malaria and its complications is present, severe orcomplicated malaria can occur.However , severe hemolytic & infarctive crises are anticipatedif patients with sickle cell diseases get Malaria
Prevalence of haemoglobinopathiesThe World Health Organization )WHO( estimates thatglobally at least : approximately 5% of adults are carriersfor a haemoglobin condition 2.9% for thalassaemia and2.3% for sickle cell diseasesCarriers are found allover the word because as a result ofmigration the populations of different ethnic groups todifferent regions of the world.
SITUATION in AfricaThe highest prevalence of sickle-cell trait is in parts ofAfrica & among people with origins in equatorial Africa, theMediterranean basin and Saudi Arabia. In Africa, the highestprevalence of sickle-cell trait occurs between latitudes 15° Northand 20° South
Over 300 000 children are born each year with a severehaemoglobinopathy. 30% are born with thalassaemiasyndromes while 70% have sickle-cell anaemiaWith worldwide migration, these diseases are as much afeature of Europe, the United States and Australia as of the.countries where they originatedPrevalence varies from under 0.1 births per 1,000 in someparts of the world to more than 20 per 1,000 in parts of Africa.In America, approximately 70,000- 80,000 people sufferfrom sickle cell disease . They are mainly of African Origin
:The situation in KSA In a study carried in KSA ,the incidence of hemoglobulin Sfor 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 milderwhereas in the western provinces the disease is severe andsimilar to that reported in African populations
In Bahrain Genetic disorders of haemoglobin are prevalent.In a study of the hospital population coveringBahrainis, 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 fromEastern Province, Saudi Arabia, where the mild form of thedisease predominates
Sickle-cell disease in Bahrain and Saudi Arabia presentsspecial features. SCD in this area is clinically mild, and. mortality is low in both children and adultsHowever, 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%(
National Control program for haemoglobinopathies:The development of appropriate national control programmeis now accepted and introduced in many parts of Asia suchas in Bahrain, the Islamic Republic of Iran and Saudi Arabia.China, India, Indonesia, Malaysia, Maldives, Singapore andThailand.
The control program depends on the characteristics & therequirements 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.
National Control program for sickle cell diseases1- 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 acid3-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(
The antenatal screening programmeParent screening for sickle cell and thalassaemia aims to• identify women/couples at risk of a pregnancy with sickle cell orthalassaemia disorders and• provide appropriate referral & care for prenatal diagnosis withcontinuation or termination of pregnancy according to women’schoices.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 severeform of the disease die before the age of five from infectionor severe anaemia
Pregnancy ANTENATAL SCREENING Offer screening Negative ResultBlood sent to laboratory for haemoglobinopathy Screen Information: No further action Positive resultsInformation & counseling-Offer partner screening Partner screening Negative ResultBlood 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
Premarital diagnosis :In the Saudi society, consanguineous marriages are high)60%(.Recently, the Saudi government introduced a newlegislation regarding premarital testing for the 2 commongenetic disorders; namely, sickle cell trait and thalassemia.The advantage of premarital diagnosis is that : affectedbirths could be prevented if couples at risk were identified.
NEONATAL SCREENINGThe newborn sickle cell screening is part of the existingbloodspot programme for Phenylketonurea )PKU( andcongenital hypothyroidism )CHT(.Neonatal haemoglobinopathy screening primarily aims toidentify infants with SCDs , in order to start prophylacticantibiotic therapy and vaccination ) Pneumococcalvaccine( as early as possible.detects carriers. For each baby detected with SCDs,neonatal screening detects between 17 and 100 sickle cellcarrier babies. Parents of a carrier child should beinformed about the carrier result
In UAE, a standard form for neonatal screening is issued to every babyborn hospital, where 99% of deliveries occur, and mothers are informed.about the procedures &importance of neonatal screening .in January 1995 by screening for Phenylketonureain January 1998. Screening for congenital hypothyroidismIn January 2002, the Ministry of Health decided to launch a pilotstudy for neonatal screening of sickle cell disease before expanding it.at the national levelNewborn infants are brought to MCH centre on the fifth day for collectionof blood samples by heel prick onto filter paperThe 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 prophylacticpenicillin by the age of 2 months and follow-up was arranged with the.cooperation of haematologist
Genetic counselingIt is the process through which knowledge about the geneticaspects of illnesses is shared by trained professionals withthose who are at an increased risk or either having a geneticdisorders or having them to be passed to their unbornoffspring.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 consequencesThe family physician usually handles most of the geneticcounseling during routine clinical visits
A survey of 500 parents, with children who have a geneticdiseases was carried, to find their knowledge about geneticdiseases indicated that the majorities were unaware ofetiologies, symptoms, inheritance and therapies.This was particularly true for parents with lower education.Until recently a genetic counselor only advised ofpossibilities of recurrence of such a disease in the family.The new policy of genetic counseling is to help the family inmaking the correct decision for preventing the disease inthe extended family and the prevention of a similarcondition in future pregnancies.
Pneumococcal diseases in children with Sickle celldisorders :•Children with sickle cell anaemia have an increasedsusceptibility to severe bacteria infection, particularly fromStreptococcus pneumoniae. The risk of infection is greater inthe first 3 years of life specially at4 months.•The incidence of Pneumococcal diseases for children withsickle cell disease is 18.4cases per 100 patients/yearcompared with 0.02 to 0.06 patientss per 100 healthy children/year•This infection may be the first clinical manifestation ofdisease and carries .•The case fatality rate of Pneumococcal diseases in thesechildren is 30%
Age distribution of pneumococcal bacteremia in children withsickle cell disease or HIV and healthy children at BostonMedical Center, 1981–1998 .9
The Risk Factors for Recurrent Pneumonia in Childrenwhich include: •Sickle-cell diseases •Impaired immune system( HIV, cancer, leukemia ) •Viral respiratory Infections •Gastroesophageal reflux disorder •Inborn lung or heart defects •Asthma
•The causative agents : Streptococcus pneumonia• Children under 2 years old are at highest risk for seriousdisease.•The organisms spread from person to person through closecontact.•Pneumococcal infections can be hard to treat because thebacteria have become resistant to some of the drugs that havebeen used to treat them. This makes prevention ofPneumococcal infections is more important.
Pneumococcal vaccine can help prevent seriousPneumococcal disease, such as pneumonia, bronchitismeningitis and septicemia & ear infections.
:There are two types of Pneumococcal vaccinePneumococcal polysaccharide vaccine )PPV( -1 containspurified capsular polysaccharide from each of 23 serotypesof Pneumococcal bacteriaPneumococcal conjugate vaccine )PCV( contains-2 capsularpolysaccharide from seven serotypes of Pneumococcalbacteria conjugated to proteinThe vaccines are inactivated, do not contain liveorganisms and cannot cause the diseases against which they.protect
)Pneumococcal polysaccharide vaccine )PPV Adults develop a good antibody response to a single dose ofPPV by the third week following immunization. Not used in children < two years of age because of poorantibody responses .The overall efficacy in preventing Pneumococcal bacteraemia is50 to 70%Post-immunization antibody levels begin to wane after five years
)Pneumococcal conjugate vaccine )PCVThe antibody response in young children can be improved byconjugating the polysaccharide to proteins. The conjugated. vaccine is immunogenic in childrenThe efficacy is 97% after giving the fourth doseThe 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 monthSecond dose of 0.5ml, at 4th monthA third dose of 0.5ml at 6th monthThe fourth dose of 0.5ml at 13th monthSubcutaneous at anterolateral thighChildren over one year of age and under five years of age:(A single dose of 0.5ml of PCV (subcutaneous upper arm
In general the Pneumococcal vaccine should begiven 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:
:Infants under one year of age Give PCV vaccine as routinely recommended at two and fourmonths of age with a booster dose at around 13 months ofage.Children aged 12 months to > five yearsIf they have a single dose of PCV before ,they should receivea second dose of PCV ( Separated by two months( becausethey may have a reduced immune response for the first dose.of the vaccineAt-risk children aged five years and overPCV is not recommended .
Don‘t give thePCV vaccine to Children had a serious )life-threatening( allergic reaction to a previous dose of this)vaccine ) as it contains proteinGive the PCV vaccine to Children even with minorillnesses, such as mild fever or diarrheaPostponed the PCV vaccine for children who aremoderately or severely ill .Wait until they recover beforegetting the vaccine
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 anorexiaSo far, no serious reactions have been associated with thisvaccine.