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European Journal of Public Health, Vol. 24, Supplement 1, 2014, 57–63
? The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
doi:10.1093/eurpub/cku104
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Consanguinity and genetic diseases in North Africa and
immigrants to Europe
Wagida A. Anwar1, Meriem Khyatti2, Kari Hemminki3,4
1 Community Medicine Department, Ain Shams University, Cairo, Egypt
2 Pasteur Institute of Morocco, Casablanca, Morocco
3 Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany
4 Center for Primary Health Care Research, Lund University, 205 02, Malmo ¨, Sweden
Correspondence: Wagida A. Anwar, Department of Community, Environmental and Occupational Medicine, Faculty of
Medicine Ain Shams University, Ramsses street, Abassya, Cairo, Egypt. Tel: +20 224837888, Fax: +20 224837888,
e-mail: wagidaanwar@gmail.com
Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal
with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to
inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of
marriage between close relatives originating from a common ancestor. With limited natural selection, recessive
genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common
in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29–33% in Morocco.
As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia
and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are
common in NA, but with immigration they have spread to Europe and to other parts of the world. Another
example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion
from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country,
and there is no evidence that any native Swede would have been diagnosed with this disease. The examples
discussed in this chapter show that the historic movement of populations and current immigration are influencing
the concept of ‘endemic’ disease.
.........................................................................................................
Introduction
E
factors shared by people in the cluster. Infectious diseases are the
most obvious environmental factors for disease clustering; these are
discussed in a specific chapter in this volume. Infectious agents also
cause some cancers, which are referred to in a separate chapter in this
volume. Other environmental factors that may cause endemic diseases
are dietary, residential and lifestyle-related factors shared by a defined
population, including dietary deficiencies or ingested toxic substances,
environmental pollution, and unhealthy customs and habits. Many of
these predisposingfactors arelikelytochange when residential circum-
stances change, for example, upon moving or emigration.
A small defined population often shares genes because of
inbreeding and eventually consanguinity (derived from a Latin
word ‘blood relation’), implying sharing of genetic heritage
because of marriage between close relatives originating from a
common ancestor (i.e., mating of relatives). With limited natural
selection, recessive genes may become more frequent in an inbred
compared with an outbred population. In European history, already
the Roman civil law prohibited a marriage if the couple was within
four degrees of consanguinity. Such prohibitions were also adopted
by the church. However, the rules did not reach all of Europe, and
consanguinity has been common particularly in cultural and
geographic isolates. European nobility kept itself above the
common law, and interrelated marriages were convenient in
consolidating class, land and power. In many other cultures, rules
were enacted against marriage between relatives, while in some
others inbreeding has been and still is commonplace. In some
large populations of Asia and Africa 20 to 50% of all marriages,
and in certain areas of Pakistan most marriages have been consan-
guineous.1The reasons to practice inbreeding at a large scale include
religion and culture, socio-economic class and royalty, and
geographic isolation and small populations.
ndemic disease clusters are caused by environmental and genetic
Inbreedingisconsidered aproblembecause itincreases the chances
of receiving deleterious recessive genes (i.e., two mutated copies,
alleles, required to cause disease) inherited from a common
ancestor. Inbreeding coefficient is defined as the probability of
receiving two copies (one from mother and the other from father)
of the same ancestral gene, which are identical by decent. The coeffi-
cient is 1/16 for first cousins and 1/64 for second cousins. Persons
with genetic diseases may be seriously handicapped and unable to
breed. Dominant alleles (only one disease allele required to cause
disease) often cause disease at early age, and the disease alleles tend
to disappear from the population because of selection during con-
secutive generations. Recessive diseases are insidious because carriers
of single disease alleles are healthy and they may reproduce normally
even though disease alleles are usually a selective disadvantage.
Affected are only some children (by average 25%) of the parents,
both of whom are carriers of the disease allele. In outbred popula-
tions, recessive disease alleles are usually rare becausethey are selected
against over generations; thus, the likelihood of inheriting two
recessive disease alleles is low. In inbred populations, the selection
against deleterious alleles is less efficient because they are
reintroduced into decedents a few generations later. The literature
on human genetics is full of examples on rare genetic diseases in
inbred populations, which were geographically isolated (e.g., Finns
and French Canadians) or cultural distinct (Ashkenazi Jews).1–4
Curiously, despite the ancient rules against consanguinity, the
scientific evidence on the deleterious effects has been relatively
recent. The first reports were published at the time of Charles
Darwin in the mid-1800s. He had a personal reason to be upset and
to demand scientific evidence because he married his first cousin.
Darwin remained sceptical, and all his 10 children were healthy.
In the present chapter, we discuss consanguinity in North Africa
(NA) and other parts of the world, and some of its deleterious
consequences in indigenous and immigrant populations. It should
be noted that many immigrant communities, at least in Europe, are
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quite inbred partly because of their cultural isolation and partly
because the immigrants constituted close relatives who then settled
in their own communities. For example, in the UK, it is estimated
that more than half of marriages of some Pakistani Muslim
immigrants are between first cousins. NA is also an endemic area
for deleterious recessive diseases, which are very common in the
population, including sickle cell anaemia and thalassaemia. The
mechanism for such recessive diseases was a puzzle to population
geneticists, who were used to the paradigm that pathological
conditions have a selective disadvantage. The measure relating to
selection was ‘fitness’, and individuals with deleterious mutations
would have less than optimal fitness. Infections, particularly before
reproduction, were considered the main selective force. Sickle cell
anaemia taught another paradigm of fitness and recessive diseases
because the disease provided a survival advantage in regions where
malaria was endemic.
Consanguinity in NA
Consanguineous marriages have been practiced since the early
existence of modern humans. At present, ?20% of world popula-
tions live in communities with a preference for consanguineous
marriage.5Consanguinity rates vary from one population to
another depending on religion, culture and geography. Noticeably,
many Arab countries display some of the highest rates of consan-
guineous marriages.6As can be seen from figure 1, an important
cluster of countries with high levels of consanguinity is observed in
most communities of NA, the Middle East and West Asia, a
transverse belt that runs from Pakistan and Afghanistan in the east
to Morocco in the west, and in South India, with intra-familial
unions collectively accounting for 20–50+% of all marriages.6The
highest consanguinity rates were reported among Pakistan army
personnel and isolated Egyptian Nubians (76 and 80.4%, respect-
ively). First cousin unions are especially popular, comprising 20–
30% of all marriages in some populations, in particular, the
paternal parallel subtype in Arab societies.6Contrary to common
opinion, consanguinity is not confined to Muslim communities. In
NA and the Middle East, for example, marriages between relatives
are also observed among Christians and Jews. It has been argued that
consanguinity must be seen as a cultural rather than an Islamic or
religious trait.
Marriage choice and decision-making is a complex interaction of
various social and cultural patterns of behaviour and norms. The main
reasons for a preference for consanguineous unions are historical,
cultural, socio-economic and geographical. Consanguineous unions
are estimated to represent 40 to 49% and 29 to 33% of all marriages
in Tunisia and Morocco, respectively. In Algeria, data from the 2007
survey showed that 39% of marriages in the sample population were
between cousins. Similar estimates have been reported from the
Tlemcen region of West Algeria. In Egypt, prevalence figures for con-
sanguineous unions ranged from 20 to 33% across different studies
and 39% as determined by the National Population Council. The
prevalence of consanguineous unions also varies by place of
residence in Egypt. It ranges from 25.4% in Lower Egypt to 55.2%
in Upper Egypt.
Estimates indicate that first-cousin marriages are approximately
two-thirds of all consanguineous marriages in Morocco and 40% in
Algeria. Close consanguinity accounts for 22% of the total marriages
in Egypt and is higher in rural areas. A consanguinity rate of 32%
with first cousin unions was observed in Tunisia. In Morocco, it
(parallel and cross cousins) accounts for 42% of all consanguineous
union. Similarly, in Egypt, the husband was more likely to be a
relative from the father’s side than the mother’s side (14 and 8%,
respectively). Surprisingly, it has been recently reported that unlike
Figure 1 Global prevalence of consanguinity as cited by Bittles AH, Black ML (ref. 6: reproduced with permission from http://www.consang.
net/index.php/Global_prevalence)
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the previous generations, paternal first-cousin marriages in Algeria
were lower than the paternal first cousin subtype in the new
generation.
Generally, the highest rates of marriages to close relatives are
consistently reported in lower educational and socio-economic
groups, the traditionally religious and the early married; the rates
tend to decline with modernization; however, not in all popula-
tions.6Reports from North African countries have shown that con-
sanguinity rates are lower in urban compared with those in rural
settings. Urban to rural first cousin rates in Egypt were 8.3 and
17.2%, respectively. The highest level of consanguineous marriage
was found in rural Upper Egypt. Likewise, the frequency of unions
between relatives was lower in the urban than in the rural areas in
Morocco (25.9 and 33.3%) and Algeria (30.6 and 40.5%). For
Morocco immigrants, ethnicity (distinction Berber vs. Arab) is a
better predictor of consanguineous marriage than the region of
origin, as Berbers in Belgium are more often married to a relative
than Arabs. The higher the level of education of the female partner,
the lower is the consanguinity rate. In Egypt, for example, a woman’s
chance of marrying a relative decreased from 35% among women
who had never attended school to 23% among women with a higher
education level. The comparable figure for Algeria was 58% in
non-educated women and 7% in highly educated women.
According to two different studies, only 6.3 to 7% of highly
educated females would marry their first cousins, whereas 12 to
15% of highly educated males tend to marry first cousins. Similar
trends of lower consanguinity rates among educated women, but not
educated men, were noticed in Tunisia and Morocco.7In a
Moroccan multinomial logistic analysis, considering variables
education and residence, it was shown that women’s education
was found to be the most significant variable in distinguishing kin
groups from the outbred. The more urbanized the place was, the
lower the consanguinity rate.
Variable secular trends in the consanguinity rates have been
noticed in most North African populations. In Algeria, for
example, consanguinity rates are increasing in the current
generation (from 32 in the old generation to 40% in the new gen-
eration),8while in others such as Egypt and Tunisia the frequency of
consanguineous marriage may be decreasing. According to two
Moroccan surveys from 1987 and 1992, the prevalence of consan-
guineous marriages declined by 4 percentage points. Amongst the
contributing factors are the increasing higher female education
levels, the declining fertility resulting in lower numbers of suitable
relatives to marry, mobility from rural to urban settings and the
improving economic status. On the other side, social, religious,
cultural, political and economic factors still play important roles
in favouring consanguineous marriages among the new generations,
just as strongly as they did among the older generations particu-
larly in rural areas.9As previously suggested by different authors,
consanguinity rates are not declining in some North African
countries because it is generally accepted that the social advantages
of consanguinity outweigh the disadvantages, and consanguinity is
regarded as a deeply rooted cultural trend. It is believed that the
practice of consanguinity has significant social and economic
advantages.9
In Europe, although the practice of consanguineous marriages has
almost completely disappeared in the main population, the trend of
intermarriages among ethnic minorities exists. With a tradition of
consanguineous marriage is maintained, for instance, people of
North African origin in France and Belgium, or people of Turkish
origin in Germany and the Scandinavian countries. This tendency is
facilitated by constraints imposed by migration, disintegration and
cultural diversity. Indeed, ethnic minorities face two problems: the
limited availability of suitable persons in the restricted local
community and the fact that their circle of acquaintance in the
country of origin tends to shrink within the limits of the extended
family. Immigration into a new country often progresses stepwise,
and after the first successful settlement, other family members follow
and soon a clan has been established in the new country. This is also
promoted by immigration legislation, which gives family members a
favoured status of entrance. Among many immigrant groups, it is
common that young men fetch a wife from the home country, and
for natural reasons the designated bride is a family member.
Among first cousins, the spouses share one-eight of their genes
inherited from a common ancestor, and so their progeny are
homozygous (or more correctly autozygous) at 1/16 of all loci.
The progeny are predicted to have inherited identical gene copies
from each parent at 6.25% of all gene loci, and this figure is far above
the baseline level of homozygosity in the general population. An
increase in the rate of homozygotes for autosomal recessive disease
genes, manifesting often in childhood, is therefore the result of
consanguinity.
Sickle cell anaemia and thalassaemia
According to data of the Catalogue of Transmission Genetics in
Arabs database on genetic disorders in Arab populations, there is a
relative abundance of recessive disorders in the Middle Eastern and
North African regions relating to the practice of consanguinity.
Thalassaemias and sickle cell diseases/anaemia (SCD) constitute
the most common inherited recessive haemoglobin disorders in
the world: ?3–7% of the global population carries an abnormal
haemoglobin gene, and 400000 affected children are born each
year. Initially described in the tropical and subtropical regions,
these diseases are now common all around the world because of
migration. According to 2010 estimates, high SCD allele frequencies
are found across most of sub-Saharan Africa, Middle East and India,
and following migrations to Western Europe and the eastern coast of
the Americas. The global number of neonates affected by haemoglo-
bin S (HbS) included 5.5 million heterozygotes and >300000 homo-
zygotes.10Beta-thalassaemia is frequently identified in subjects from
the Mediterranean area (Italy, Sardinia, Sicily, Greece and NA), but
it is also found in patients coming from Africa and parts of Asia
(Iran, India, Vietnam and Thailand). It is estimated that ?60000
children are born with beta-thalassaemia.11
SCD is caused by a point mutation at the sixth position of the
beta-globin chain, causing glutamic acid to be replaced with valine.
In SCD, haemoglobin two wild-type alpha-globin subunits are
associated with two mutant beta-globin subunits to forms HbS.
Under low-oxygen conditions, HbS has a tendency to aggregate,
which distorts red cells into a sickle shape. SCD is characterized
primarily by chronic anaemia and periodic episodes of pain. This
leads to further slowing of circulation, reduction in oxygen tension
and more red cells sickling and an eventual blockage of a vessel. The
blockage is the cause of the painful crisis characterizing SCD.
Thalassaemia is caused by a variant or missing globin gene. In
beta-thalassaemia, there is a reduced or absent production of beta-
globin, encoded by a single gene on chromosome 11. In alpha-
thalassaemia, the defect is in alpha-globin genes but because there
are two copies of them in different chromosomes, usually only one is
defective. A child born with thalassaemia major has two defective
alleles for beta-chain gene and he is homozygous for beta thalassae-
mia. The individual with thalassaemia minor has only one copy of
the defective beta-globin gene and he is heterozygous for beta thal-
assaemia. Thalassaemia major causes a marked deficiency in
beta-chain production, leading to severe anaemia with sequelae
such as retarded growth, bone deformities, reduced energy gener-
ation—and ultimately death at a young age. Persons with thalassae-
mia minor have mild anaemia or none at all, and no treatment is
necessary.
In Tunisia, the average frequency of SCD is 1.9%; it is between 0.8
and 3.5% in Algeria and 1.2% in Morocco.11,12In Egypt, along the
Nile Valley, the HbS gene is almost non-existent, but in the western
desert near the Libyan border, variable rates of 0.4% in the coastal
areas to 9.0% in the New Valley oases have been reported. In North
Consanguinity and genetic diseases
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African countries, most SCD patients have a severe disease, though
cases with the mild form have also been reported.12For thalassae-
mia, epidemiological data show that in the East Mediterranean
region, the carrier rate ranges between 1.5 and 6% of the total
population. The carrier rates are 1.5 to 3.0% in the Maghreb
countries and higher at 5–9% in Egypt.11,13Alpha-thalassaemia is
found mainly in populations of Southeast Asia, the Mediterranean
Basin and Central African countries. The incidence has been
reported at 5% in Tunisia, 9.0% in Algeria and 2% in Morocco.11,13
Genetic studies have found that thalassaemia mutations show
heterogeneity in NA, especially between Algeria, Tunisia and
Morocco, which could be explained by new mutational events and
gene flow due to human migrations and colonization.13Among the
>45 mutations identified in the beta-globin gene in North African
countries, the most common in Tunisia and in Algeria is codon 39
(C>T) and IVS-I-110 (G>A), accounting for >50% of all
mutations. In Morocco, the predominant mutations are at codon
39 and frameshift codon 8 (–AA) (11). The codon 39 mutation is
most common in the western part of NA compared with the eastern
part of the Mediterranean Basin, while the IVS-I-110 mutation is
more common in the Eastern Mediterranean region. Studies of
globin gene haplotypes have been used to trace the origins and
timing of the mutations and their subsequent flow. For the codon
39 mutation, an occidental and ancient origin is predicted with
introduction into the Maghreb during the Roman period through
Italy and Spain. For IVS-I-110, an Eastern Mediterranean origin is
likely.13It could have been introduced in Tunisia and Algeria during
the Ottoman rule in the 17th century.14Evidence suggests that the
North African HbS mutation originates from Central West Africa
(Benin), where it arose ?3000 years ago. Carriers of this allele later
travelled across the then fertile Sahara to the North. The arrival of
the carriers to NA was probably more recent and could follow forced
migrations from black Africa through slavery roads and/or to the
continuous influx of sub-Saharan Africans through the caravan
routes.
A UK study found 68 different beta-thalassaemia mutations in
antenatal diagnostics, and of these mutations, 59 were found in
immigrants. A total of 40 different alpha-thalassaemia mutations
were found, including all the Southeast Asian and Mediterranean
alpha-thalassaemia mutations.14
Periodic fever syndromes
The periodic fever syndromes (also known as autoinflammatory
syndromes) are diverse disorders, which are caused by dysfunction
of the inflammasome complex of the innate immune system.15,16As
the mechanisms controlling inflammation are disturbed, the result is
an uncontrolled inflammation throughout the body manifesting as
high recurring fever, joint and abdominal pains, and amyloidosis as
a chronic complication. Hereditary periodic fever syndromes include
pyrin-associated familial Mediterranean fever (FMF), cryopyrin-
associated periodic syndrome, mevalonate kinase deficiency and
tumour necrosis factor receptor-associated periodic syndrome.15
However, because FMF is the most common hereditary syndrome,
we will focus on this disease.17FMF is common in the Eastern
Mediterranean area but rare elsewhere, as are the other periodic
fever syndromes. Many of these diseases are diagnosed by paediatri-
cians and, for example, 80% of FMF cases occur before the age of 20
years.15FMF is, according to a review, almost always restricted to
Turks, Armenians, Arabs and non-Ashkenazi Jews or emigrants with
these ethnicities and, according to this source, no cases have been
described in individuals of Scandinavian origin.18Autoinflammatory
conditions may give rise to reactive amyloidosis, which may
manifest initially as renal problems; the amyloid precursor is
serum amyloid A, the normal and not a mutated protein.15,16,18–20
The kidneys and the gastrointestinal tract are the vulnerable organs
when the patients have developed amyloidosis.15,21,22However, the
development of amyloidosis in hereditary autoinflammatory disease
patients depends on the severity of the condition and may be rare in
patients responding to treatment, which for FMF includes
colchicines.18,23,24
We recently carried out a nation-wide study on diseases in
Sweden.25Patients were identified from the Swedish Hospital
Discharge Register and from the Outpatient Register for 2001
through 2008. Familial autoinflammatory disease was diagnosed in
210 patients, with an incidence of 2.83 per million. At least 98% of
the patients were immigrants, most of whom were from the Eastern
Mediterranean area. Young Syrian descendants had the highest
incidence rate, which was >500-fold higher than that in individuals
with Swedish parents. Even the early onset of these conditions
identifiedthemasfamilialautoinflammatory
concluded that familial autoinflammatory disease was brought into
the country as a result of immigration, mainly from the Eastern
Mediterranean area. Although we could not specify the diagnosis,
all indications suggested that it was FMF. This was a rather
remarkable example on how population movements may bring
forth new medical problems. There had been no previous
literature on FMF being diagnosed in Sweden. A European registry
onautoinflammatorydiseases
monogenic diseases, but it reported only one patient in Sweden
and without diagnostic details.17However, concurrent to our pub-
lication, another study appeared from Sweden that reported 37 FMF
patients originating from the Eastern Mediterranean area; none of
them were of Swedish origin.26Our conclusion about the origins of
the 210 patients, which probably included the 37 FMP patients, was
that there was no evidence of any patient with a Swedish origin.25
Reports on FMF patients in other European countries have started
to appear. Germany has a large Turkish immigrant population, and
most FMF patients had a Turkish origin.27–29An incidence of 55 per
million was estimated for children of the Turkish origin. This
compared our estimate of 140 per million for Syrian descendants.25
In endemic areas, rates have been estimated to be as high as 1000 per
million.18
diseases. We
included 1049patients with
Diabetes mellitus
The two most common forms of diabetes are type 1 diabetes (T1D),
previously known as insulin-dependent diabetes, and type 2 diabetes
(T2D), previously known as non-insulin-dependent diabetes. Both
types are caused by a combination of genetic and environmental risk
factors. Diabetes mellitus is a chronic debilitating disease defined as
a group of heterogeneous disorders with the common elements of
chronic hyperglycaemia and glucose intolerance due to insulin
deficiency, impaired effective of insulin action or both.30Diabetes
is now one of the most common non-communicable diseases
globally. It is the fourth or fifth leading cause of death in most
high-income countries, and it is epidemic in many low- and
middle-income countries.31
T1D is caused by the autoimmune destruction of the beta cells of
the pancreas, and represents ?10% of all cases with diabetes. The
incidence of T1D is increasing worldwide at a rate of ?3% per year.
The recent increase in T1D incidence points to a changing global
environment rather than variation in the gene pool, which require
the passage of multiple generations.32Recent prospective studies are
helping to elucidate the role of viruses to the aetiology of T1D.
For example, enteroviral infections occurring as early as in utero
appear to increase a child’s subsequent risk of developing
the disease.33Other viruses, including mumps,34cytomegalovirus,
rotavirus35and rubella,36have also been associated with the disease.
First-degree relatives have a higher risk of developing T1D than
unrelated individuals from the general population (?6 vs. <1%,
respectively). These data suggest that genetic factors are involved
with the development of the disease. At present, there is evidence
that >20 regions of the genome may be involved in genetic
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susceptibility to T1D. However, none of the candidates identified
have a greater influence on T1D risk than that conferred by genes in
the human leucocyte antigen (HLA) region of chromosome 6. This
region contains several hundred genes known to be involved in
immune response. Those most strongly associated with the disease
are the HLA class II genes (i.e., HLA-DR, DQ and DP), contributing
?40–50% of the heritable risk for T1D, but even non-HLA genes
have been implicated.37–39
T2D is the most common form of the disease, accounting for
?90% of all affected individuals. It is caused by relative impaired
insulin secretion and peripheral insulin resistance. Typically, T2D is
managed with diet, exercise, oral hypoglycaemic agents and
sometimes exogenous insulin. In 2000, it is estimated that 171
million people (2.8% of the world’s population) had diabetes and
that by 2030 this number will be 366 million (4.4% of the world’s
population). It has long been known that T2D is, in part, inherited.
Family studies have revealed that first-degree relatives of individuals
with T2D are ?3 times more likely to develop the disease than
individuals without a positive family history of the disease.40To
date, >50 candidate genes for T2D have been studied in various
populations worldwide.41
Three of the world’s top 10 countries with the highest prevalence
(%) of diabetes are in the Middle East and NA (MENA) region:
Saudi Arabia, Kuwait and Qatar. The MENA region has the
highest comparative prevalence of diabetes (10.9%). According to
the latest estimates, 35 million people, or 9.2% of the adult
population, have diabetes. This number is set to almost double to
68 million by 2035.31,32Diabetes in the MENA region is mainly T2D.
The number of people with impaired fasting glucose is estimated to
be 25.2 million people, or 6.7% of the population, who are therefore
at high risk of developing diabetes.42The highest prevalence
of impaired glucose tolerance (13.1%) was found in rural Egypt,
and the lowest prevalence was found in rural Sudan with a
prevalence of 2.2%. One study in Tunisia reported on impaired
fasting glucose, and the prevalence was 5.3% in men and 5.1% in
women. Through reviewing 12 community-based studies, the
prevalence of undiagnosed diabetes ranged from 18% in urban
Libya to 75% in Tunisia. The prevalence of diabetes varied across
North African countries, and it was found that the prevalence in
urban areas than in rural areas range from 2.6% in rural Sudan to
20% in urban Egypt.43–45Diabetes mortality estimated to be >10%
of all adults in the MENA region, i.e. 368000 deaths with 146000
men and 222000 women in 2013.42
Diabetes in immigrants from Africa is high as in African
Americans (12–15%), closely followed by Caribbeans of African
descent and low among indigenous African origin populations
(1–6%). In the African diabetes, majority of cases are T1D
(70–90%), followed by T1D (5–20%) and atypical presentation
accounts for 5–15%.46There are limited data on T1D among
African, but is becoming increasingly more prevalent and the
available evidence suggests that in African the age of onset occurs
later than in the developed world.47
According to a systematic review, the prevalence of retinopathy
ranged from 8.1% in Tunisia to 41.5% in Egypt. Albuminuria
prevalence ranged from 21% in Egypt to 22% in Sudan;
nephropathy ranged from 6.7% in hospital outpatient clinics in
Egypt to 46.3% in hospital inpatients in Egypt. The prevalence of
diabetic neuropathy ranged from 21.9% in hospital outpatient
clinics to 60% in hospital inpatient clinics in Egypt.43The impact
of increasing prevalence of diabetes is translated into severe
economic burden, high morbidity and mortality rates.48Effectively
the economic capabilities of the health care system in most of Africa
countries are not sufficient to withstand the burden of diabetes
effective. Thus, sustainable strategies are needed to promote
diabetes awareness and public health policies that empower individ-
uals to diabetes self-management to improve the quality of life,
reduce morbidity and premature mortality.49,50
Rare recessive diseases
North African and Middle Eastern populations share disease alleles,
for example, the Tunisian population shares founder mutations with
other North African and Middle Eastern populations for 43
inherited conditions. Founder chromosomal segments described in
Tunisian patients with Meckel syndrome (characterized by renal
cystic dysplasia), sickle cell anaemia and xeroderma pigmentosum
(XP) group A (XPA) are identical to those described in Algerian
patients.51
Thefoundermutations
polyposis of the colon and the hepatocerebral mitochondrial DNA
depletion syndrome are reported on the same haplotypes between
TunisianandMoroccanpatients.52
Moroccan patients share haplotypes for autosomal recessive
non-syndromic optic atrophy, Bare lymphocyte syndrome and for
the major founder mutation p.R228X in XPA—beta-thalassaemia
and FMF were discussed earlier.51
Severe childhood autosomal recessive muscular dystrophy is the
most frequent muscular dystrophy in Tunisia, and most patients are
homozygous for founder mutation c.del521T mutation in SGCG
gene.53The recurrent mutation p.V548AfsX25 in the XPC gene
and leading to XPC, a rare severe genodermatosis associated with
skin tumours, was first described in Algerian and Moroccan patients
at homozygous state.54For Hurler syndrome, also known as
mucopolysaccharidosis type I and often classified as a lysosomal
storage disease, is caused by a defective IDUA gene, encoding
iduronidase enzyme. Over 50 different mutations in the IDUA
gene have been shown to cause Hurler syndrome. Point mutation
P533R is a founder mutation in the Tunisian population and it is
frequent in all the Maghrebian populations even in the Maghrebian
immigrant population in France.51For congenital myasthenic
syndrome, patients originating from four North African countries
and living in France share the same haplotype bearing the
c.1293insG mutation affecting the CHRNE gene.55The strong
evidence for a single ancestral founder event in the North African
populationsimplifiesdiagnostics
syndrome.56Cystic fibrosis (CF), also known as mucoviscidosis, is
an autosomal recessive genetic disorder that not only most critically
affects the lungs, but also the pancreas, liver and intestine.57CF is
caused by a frameshift mutation in the gene for the protein CF
transmembrane conductance regulator, regulating the movement
of chloride and sodium ions across epithelial membranes and
influencingthe composition of sweat, digestive fluids and
mucus.58CF is diagnosed in males and females equally, but for
unknown reasons males tend to have a longer life expectancy than
females.59
The geographic distribution of 272 CF mutations was studied by
assessing the origin of 27177 CF chromosomes in 29 European and
3 North African countries. The most common mutations are delta
F308 (66.8%), G542X (2.6%), N1303K (1.6%), G551D (1.5%) and
W1282X (1.0%). The delta F508 mutation has the highest frequency
in Denmark (87.2%) and the lowest in Algeria (26.3%). Mutation
G542X is common in Mediterranean countries, with a mean
frequency of 6.1%. N1303K is found in most of the Western and
Mediterranean countries and has the highest frequency in Tunisia
(17.2%). G551D is common in north-west and central Europe, but is
uncommon in other parts of Europe. W1282X has the highest
frequency in Israel (36.2%), being also common in most
Mediterranean countries and NA.60The wide distribution of these
mutations suggests an ancient origin.
Triple A syndrome (Allgrove syndrome) is a highly heterogeneous
autosomal recessive disorder with high lethality. It is associated with
mutations in the AAAS gene, which encodes a protein known as
aladin. Both the geographical distribution of carriers of the
mutation (Algeria and Tunisia) and the size of the common
ancestral haplotype, indicate that the triple A mutation in the
North African population is very old and occurred in the ancient
Arabian population a long time before it entered NA.61
leadingtoadenomatous
Tunisian,Algerianand
ofcongenitalmyasthenic
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Conclusions
In the present chapter, we discuss consanguinity in NA, and some of
its deleterious consequences in indigenous and immigrant popula-
tions. The distribution of founder mutations is the result of
historical migratory movements, and many common disease alleles
in the current NA have origins elsewhere, but the disease burden in
NA is largely the result of inbreeding. NA has been a main source of
European immigrants, and the disease alleles have been introduced
to the national gene pools. However, for recessive diseases, the most
frequent disease manifestations are in inbred immigrant popula-
tions. It remains unclear how well European health care providers
are able to cope with the imported diseases. The example of periodic
fever syndromes showed that a new disease may be introduced into
immigrant-dense countries with little notice by the medical
community. Diagnostics of recessive disease require demonstration
of specific mutations in target gene. Thus, knowledge of the
common founder mutations in ethnic immigrant populations is
required and diagnostic tests used in NA could be applied.
Funding
The present work was funded by EUNAM (EU and North African
Migrants: Health and Health Systems, EU FP7/2007-2013 grant
260715).
Conflicts of interest: None declared.
Key points
? Consanguinity is common in NA, as a consequence,
recessive disorders are common in the region, SCD being
most prevalent, followed by thalassaemia.
? Immigration is influencing the pattern of recessive diseases
in Europe.
? These disorders are likely to be further propagated because
the habit of inbreeding is continuing in many immigrant
communities.
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