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Genetic disorders in the Arab worldLihadh Al-Gazali, Hanan Hamamy, Shaikha Al-Arrayad

Available evidence suggests that congenital andgenetic disorders are responsible for a majorproportion of infant mortality, morbidity, and handi-cap in Arab countries.1–3 The population of the regionis characterised by large family size, high maternal andpaternal age, and a high level of inbreeding withconsanguinity rates in the range of 25-60%.1 2 4 w1 Cer-tain disorders are common throughout the Arabworld, including haemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, different con-genital malformations caused by recessive genes, andseveral metabolic disorders.1 2 Other recessive dis-orders cluster in certain groups and subpopula-tions.1 2 5 Genetic services vary in extent and coveragein different Arab countries, but mostly they remainpatchy, selective, and inadequate.2 5 6

We present the magnitude of the problem and thecurrently available genetic services in Arab countries,together with recommendations for developing strate-gies for prevention. In view of the good coverage ofprimary healthcare systems in most Arab countries,community genetic services that include screeningprogrammes could be strengthened by the efficienttraining of primary healthcare personnel.2

Why are genetic disorders common inthe Arab world?Available data suggest that genetic and congenital dis-orders are more common in Arab countries than inindustrialised countries; recessively inherited disordersaccount for a substantial proportion of physical andmental handicap.1–3 6 Several factors may contributeto the high prevalence of genetically determineddisorders:x High consanguinity rates—25-60% of all marriagesare consanguineous, and the rate of first cousinmarriages is high (figs 1 and 2; table A on bmj.com).4 w1

In addition, isolated subpopulations with a high level ofinbreeding exist. Furthermore, in many parts of theArab world the society is still tribal.5 6 w1 This has madethe epidemiology of genetic disorders complicated, asmany families and tribal groups are descended from alimited number of ancestors and some conditions areconfined to specific villages, families, and tribal groups,leading to an unusual burden of genetic diseases inthese communities (table B on bmj.com)1 2 5

x The high prevalence of haemoglobinopathies,glucose-6-phosphate dehydrogenase deficiency, auto-somal recessive syndromes, and several metabolicdisorders (fig A and table C on bmj.com)1 2 5

x The rate of children with Down’s syndrome in someArab countries exceeds the 1.2-1.7 per 1000 typical forindustrialised countries. This may be related to therelatively high proportion of births to older mothers inthe region (up to 50% of children with Down’ssyndrome in the region are estimated to be born tomothers aged 40 or over)1 2 7 w3

x The lack of public health measures directed at theprevention of congenital and genetic disorders, withinadequate health care before and during pregnancy,particularly in low income countries2

x Services for the prevention and control of geneticdisorders are restricted by certain cultural, legal, andreligious limitations, such as the cultural fear offamilies with genetic diseases being stigmatised withintheir community and the legal restrictions on selectivetermination of pregnancy of an affected fetus.1 2 5 6

Summary points

The population in Arab countries is characterisedby large family size, high maternal and paternalage, and a high level of inbreeding

Genetic disorders are common in Arab countriesand account for a substantial proportion ofphysical and mental handicap

Generally, no public health measures are directedat the prevention of congenital and geneticdisorders, which is also restricted by cultural andlegal limitations

Some countries have started cost effectiveprevention programmes for certain commongenetic disorders, such as premarital carrierscreening for haemoglobinopathies

Strategies for the prevention of genetic disordersin this region should include integration ofcommunity genetics into the primary healthcaresystem, education, and strengthening the existingspecialised genetic service

Extra tables, boxes, figures, and references w1–w12 are onbmj.com

Department ofPaediatrics, Facultyof Medicine andHealth Sciences,United ArabEmirates University,Al-Ain, United ArabEmiratesLihadh Al-Gazaliprofessor in clinicalgenetics

National Center forDiabetes,Endocrinology andGenetics, Amman,JordanHanan Hamamyprofessor in humangenetics

Salmaniya MedicalComplex, Ministryof Health, Bahrain,Kingdom ofBahrainShaikha Al-Arrayadconsultant geneticist

Correspondence to:L Al-Gazalialgazali@hotmail.com

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Genetic prevention programmesDespite the difficulties that exist, several Arab countrieshave initiated cost effective prevention programmesfor certain common genetic disorders.

Premarital carrier screeningA screening programme for genetic carriers is asystematic attempt to identify and counsel as manypeople at genetic risk in a population as possible,whether or not they have a family history of a geneticdisorder. Several countries in the Arab region haveintroduced premarital screening for haemoglobino-pathies. In Saudi Arabia, a Royal decree was passed in2003 for a mandatory premarital screening testfollowed by non-directive genetic counselling forhaemoglobinopathies; the decision to marry is thenleft to the couple. Prenatal diagnosis and terminationof pregnancy are not offered to carrier couples, eventhough a 1990 ruling (Fatwa) allows termination ofpregnancy in the first 120 days after conception if thefetus is shown beyond doubt to be affected with asevere malformation that is not amenable totreatment.w4 Similar programmes exist in other Arabcountries such as Bahrain, the United Arab Emirates,Tunisia, and Jordan (box A on bmj.com).5 6 8 w5

However, experience shows that if options are notmade available to carrier couples such programmes

will not be effective in reducing the burden of geneticdiseases, as many carrier couples go ahead with theirplanned marriage.2 Arab countries should take note ofthe comprehensive primary care based programme forthalassaemia screening and genetic counselling thatwas started in 1996 in Iran (a Muslim country wheretermination of pregnancy was not legal). Theprogramme identifies carrier couples before marriageand offers counselling, thus providing them with theopportunity to separate. However, an audit in 1999showed that couples were still opting to marry ratherthan separate and that they requested prenatal diagno-sis and selective termination of pregnancy.9 Amend-ment of the law in 2001 to allow the option of selectivetermination of pregnancy up to 15 weeks’ gestation forthalassaemia resulted in a 70% reduction in the annualbirth rate of affected infants.9

Family oriented approach to preventionWhen a gene for a recessive disorder is present in afamily, the diagnosis of the disease in a child serves as amarker of the extended family that is at increasedgenetic risk. In communities where a high level of con-sanguinity exists and large families are common,family oriented screening offers an alternative topopulation screening for identifying current andfuture couples at risk of producing affected children.2 10

This approach is particularly suitable to populationswith a high level of consanguinity and clustering ofrare genetic diseases in certain tribes or families. Itproduces a high yield of information on carriers andcouples at risk, family members understand the condi-tion because they have had contact with an affectedchild, and usually one gene variant is present in a givenfamily or tribe, simplifying and reducing the cost ofDNA based diagnosis.2 10 This approach was tested inPakistan in 15 large consanguineous families with �thalassaemia and was found to be feasible. Theprogramme was successful because carriers had theoption of prenatal diagnosis and selective terminationof pregnancy, which is legal in Pakistan. A similarapproach was implemented in the Arab NegavBedouin community, where the genetic data on carrierstatus for genetic disorders common in this commu-nity were incorporated into the decision making pro-cess of arranged marriages, giving carriers the optionto choose a non-carrier partner.w6 w7

SourcesWe collected information for this report from published literature through aMedline search, from experts working in medical genetics and providinggenetic services, and from personal archives of references taken from locallypublished medical journals in Arab countries. The main documents that weused extensively as references include the World Health Organization East-ern Mediterranean Regional Office publication Community Control of Geneticand Congenital Disorders2 and the Oxford Monographs on Medical Genetics onGenetic Disorders among Arab Populations.1

Affected male Affected female Consanguineous marriage

Fig 1 Two Arab pedigrees showing high level of consanguinity,large family size, and several affected children in different sibships

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Fig 2 Average rates of marriages between first cousins amongArabs. UAE=United Arab Emirates

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Neonatal screening programmesClinical screening of newborn infants involves system-atic examination with a checklist of all births, whetheralive or stillbirths, by an experienced paediatrician todetect any abnormalities.2 The United Arab Emiratesand Oman have established national or hospital basedregistries for congenital abnormalities. Some of theseregistries report to the International Clearing Housefor Birth Defects.w8

Biochemical neonatal screening programmes in theregion have started as research projects that haveprovided valuable information on the incidence of hae-moglobin disorders, glucose-6-phosphate dehydroge-nase deficiency, congenital hypothyroidism,phenylketonuria, and cystic fibrosis.2 National screeningprogrammes for phenylketonuria (started in the UnitedArab Emirates in 1995) and for congenital hypothy-roidism (started in Saudi Arabia in 1985 and the UnitedArab Emirates in 1998) have been successful.5 11 w9

Jordan started a similar programme in certain areas in2006, with the intention of expanding it nationally.Screening of newborns for phenylketonuria in Gaza,started in 1994, covers only the government clinics,although two third of all newborns are delivered inUnited Nation Relief and Work Agency clinics where nophenylketonuria screening is offered.w10 The Emirate ofAbu Dhabi introduced screening for sickle cell diseasewith high performance liquid chromatography in 2002.5

Plans exist to make this a national programme acrossthe United Arab Emirates.

Strong evidence exists to show that metabolicdiseases constitute a significant cause of neonatal andinfant death among Arabs.1 2 Therefore, screening pro-grammes using the Guthrie system would be valuablein the prevention and early treatment of thesedisorders. Saudi Arabia has an active selective newbornscreening programme for inherited metabolic diseasesthat reaches 10-20% of newborns. Screening is basedon dried blood spot samples and tandem massspectrometry. The Saudi experience indicates thatapproximately 50% of diseases identified by thismethod are manageable.11 However, in many casestreatment does not prevent the considerable morbidity.Economic cost should also be taken into account.

Antenatal screening for chromosome abnormalitiesand congenital malformationsIn some industrialised countries, pregnant womenhave non-invasive screening for Down’s syndrome andother congenital anomalies through the assessment ofmaternal serum markers and ultrasonography ataround 11 weeks post-conception. This is followed byinvasive prenatal diagnosis if the test is positive, givingthe couple the option of selective termination of preg-nancy of an affected fetus. As termination is not legal inmany Arab countries, the value of introducing prenatalscreening programmes is questionable. A bettermethod of prevention would be the general availabilityof preconception information and family planning forolder mothers, which would be expected to lead to areduction of around 50% in the frequency of new casesof Down’s syndrome.2

Ultrasound scanning is routinely done forpregnant women during their first antenatal visit inmost Arab countries. The scan is usually done withoutany pretest information being given to the couple

about the possibility of finding an abnormality andwith no explanation of the consequences. If the resultssuggest an abnormality, the woman is referred for adetailed anomaly scan, and further invasive tech-niques, such as amniocentesis, might be needed. Thecouple will then have to face the major decision ofselective termination of a fetus affected by severegenetic or congenital disorder (see patient’s story). Inmost Arab countries, except Tunisia,w5 selective termi-nation of pregnancy is not legally available. This oftenleads to ethical dilemmas.2 5 It is therefore importantto clarify the role of ultrasonography for fetal anoma-lies in obstetric services in this region.2 5

Pre-implantation genetic diagnosisPre-implantation genetic diagnosis is welcomed inArab countries, as it does not involve the decision toterminate the pregnancy. A recent study from UnitedArab Emirates found that most people favour thismode of prevention.12 The procedure is, however, stillin its early stages, with many limitations. Pre-implantation genetic diagnosis involves assisted repro-ductive technology. It is a complex, time consuming,and expensive procedure that is available only at asmall number of centres and for a limited number ofgenetic conditions. It is available in Saudi Arabia, whereseveral single gene disorders can be diagnosed.11 w11

Various numerical chromosome aberrations such astrisomies 21, 13, and 18 and sex chromosomeabnormalities are being diagnosed in Jordan by use ofthe fluorescent in situ hybridisation technique after invitro fertilisation in a few private obstetric hospitals.6

Pre-implantation genetic diagnosis for common disor-ders such as � thalassaemia could be included in futureprevention programmes.

Role of education in preventing genetic disordersMedical genetics education assumes particular impor-tance in the region because of the high frequency of

A patient’s perspective

When I married my cousin, I thought about genetic diseases and theprobabilities of my children having those diseases. I knew that three sisterswho were distantly related to me had some problems, which I thoughtcould have happened by chance or because their mother was old when shehad them.

My first pregnancy was normal until the sixth month, when I was toldthat my baby had water in his brain. It was hard not to know what exactlywas wrong with the baby. The waiting was over when my baby was born on29 August 2002. I found that he had many congenital abnormalities. In thebeginning, the doctors did not know what the actual problem was. I laterfound out that another branch of my family had two children with similarproblems, which made me realise that my child, the three sisters, and thetwo other children all have the same condition. The geneticist explained tous that it is inherited and I have 25% risk of having another affected child. Iagreed to do genetic studies to find the gene, because I was concernedabout the next pregnancy. My second child was normal, and that was ablessing from God.

The gene was located in my family, and the geneticist told us that in thenext pregnancy the baby can be tested and terminated if found to beaffected, but I would have to go abroad for that. When I became pregnantwith my third child, I decided not to go for the test because as Muslims weconsider life itself as a test. When God gives me a child with a problem, it islike he is testing me to see how I accept, help, teach, and be patient with thischild. I am sure that in every creation in this world there is a wisdom that isknown only by God. I am six months pregnant now, and ultrasound hasshown that the baby is affected.Female patient, United Arab Emirates

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genetic disorders and the generally low genetic literacy.Inadequate numbers of specialised personnel experi-enced in medical genetics are available, genetics is notemphasised in medical curriculums, and effective teach-ing methods and integration between medical geneticsand other related clinical specialties are lacking.2 In mostArab countries, health services are delivered by anetwork of primary healthcare centres where workersare not adequately trained to deal with common geneticdisorders. They need to acquire the necessary skills infirst level counselling to provide premarital and precon-ception counselling and counselling before newbornand carrier screening (box 1). Genetic counselling forpeople or families at high risk or those withunfavourable test results is provided by the fewspecialists in the field.

The World Health Organization Eastern Mediterra-nean Regional Office publication Community Control ofGenetic and Congenital Disorders2 provides an outline ofthe basic requirements to strengthen the capabilities ofprimary healthcare workers in preventing geneticdiseases (box B on bmj.com). Recognising the need forgenetic services (fig B on bmj.com), Jordan is developinga national strategy for the prevention of genetic diseases,which includes provision of community geneticstraining and education courses for primary healthcarephysicians and nurses.6 Bahrain has started a pro-gramme for the dissemination of information throughprimary healthcare physicians.8 The service has beenstandardised, and premarital counselling has becomewidely available through all health centres. At one time,

structured courses in provision of community geneticservices were supplied to family doctors in Egypt.w12

One of the most important aspects of preventionprogrammes for genetic disorders is to have a wellinformed and educated population. Saudi Arabia, theUnited Arab Emirates, and Bahrain have introducedgenetics information, particularly on haemoglobin-opathies, to the public through health workers and pri-mary healthcare centres and through the media, but nostudies have measured the effect of such programmes.

ConclusionThe effect of genetic and congenital disorders in Arabcountries is high. Genetic services are inadequate anddo not cover all the population. Preventive strategies,summarised in box 2, should be adopted at a nationallevel, with development of regional and internationalcollaboration and with technical support from WHO.

Contributors: LA-G developed the idea, searched the literature,wrote the paper, and was responsible for the overallorganisation. HH searched the literature, helped in writing thepaper, and provided ideas on the content of the paper. SA-Asearched the literature and provided some information relevantto the paper. LA-G is the guarantor.Competing interests: None declared.

1 Teebi A, Farag T. Genetic disorders among Arab populations. New York:Oxford University Press, 1997. (Oxford Monographs on Medical Genet-ics No 30.)

2 Alwan A, Modell B. Community control of genetic and congenital disorders.Alexandria: Eastern Mediterranean Regional Office, World HealthOrganization, 1997. (EMRO Technical Publication 24.)

3 Christianson A, Howson C, Modell B. March of Dimes global report on birthdefects: the hidden toll of dying and disabled children. New York: March ofDimes, 2006.

4 Consang.net. Background summary (updated 24 May 2005).www.consang.net/summary.html (accessed 22 Aug 2006).

5 Al-Gazali LI, Alwash R, Abdulrazzaq YM. United Arab Emirate: commu-nities and community genetics. Community Genet 2005;8:186-96.

6 Hamamy H, Al-Hait S, Alwan A, Ajlouni K. Jordan: communities andcommunity genetics. Community Genet (in press).

7 Wahab AA, Bener A, Teebi AS. The incidence patterns of Down syndromein Qatar. Clin Genet 2006;69:360-2.

8 Al Arrayed S. Campaign to control genetic blood diseases in Bahrain.Community Genet 2005;8:52-5.

9 Samavat A, Modell B. Iranian national thalassaemia screeningprogramme. BMJ 2004;329:1134-7.

10 Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families forgenetic hemoglobin disorders in Pakistan. N Engl J Med 2002;347:1162-8.

11 Al-Odaib AN, Abu-Amero KK, Ozand PT, Al-Hellani AM. A new era forpreventive genetic programs in the Arabian Peninsula. Saudi Med J2003;24:1168-75.

12 Al-Gazali LI. Attitudes toward genetic counseling in the United ArabEmirates. Community Genet 2005;8:48-51.

13 Stoltenberg C, Magnus P, Skrondal A, Lie RT. Consanguinity and recur-rence risk of birth defects: a population based study. Am J Med Genet1999;89:423-8.

(Accepted 7 September 2006)

doi 10.1136/bmj.38982.704931.AE

Box 1: Premarital advice about consanguinity at the primaryhealthcare level2

• Detailed family history should be taken to spot any genetic disease• The couple should be asked about any known inherited disease in thefamily, history of birth defects, impairment of hearing or vision, learningdifficulties, any unexplained neonatal or infant deaths, and failure to thriveamong infants• If a genetic disorder is suspected in the family, the couple should bereferred to a specialised genetic counselling clinic• If no known inherited disorder exists in the family, first cousins intendingto marry are informed of the doubling of the risk for birth defects13

Box 2: Strategies for the prevention and control of genetic andcongenital disorders in the Arab world2

• Integration of community genetic services into primary healthcaresystems, such as the integration of preconception counselling and screeninginto the existing reproductive health programmes in the country; thisrequires education and training of primary health workers• Education of the public through updating high school curriculums andmass media educational campaigns that are scientifically based andappropriately delivered with respect to local cultural and religious beliefs• Strengthening human resources by updating medical and nursing collegecurriculums related to the practice of human genetics, with more emphasison practical guidelines for how to approach common genetic andcongenital disorders• Initiation of population screening programmes and national birth registries• Introducing new technology and strengthening of existing genetic service• Defining the ethical, legal, religious, and cultural factors in formulatinggenetic services, such as specific guidelines for prenatal genetic diagnosisand termination of a fetus affected by a genetic or congenital disease

Role of GPs outside the Arab world

General practitioners looking after Arab familiesoutside the Arab world should always inquire aboutthe presence and degree of consanguinity. Theyshould be familiar with its risk of increasing geneticdisorders (box 2) and be able to detect genetic risk insuch families by asking about a family history oflearning difficulties, anaemia, malformations, andhandicapping disorders. They should also be able toprovide counselling information about risk andscreening for disorders known to be common in thesecommunities, such as thalassaemia, sickle cell disease,and glucose-6-phosphate dehydrogenase deficiency.

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