In Tunisia, prevalences of different types of mucopolysaccharidoses have been evaluated: MPS global incidence was evaluated at 2.3/100.000 lives births in 2001 . Although the covering data was the widest possible, the prevalence of the MPS were undervalued and underappreciated due to ignorance of some clinical pictures by clinicians of the Tunisian public health. A national retrospective study covering the period 1970 - 2005 concerning the incidence of mucopolysaccharidoses in Tunisia, showed that prevalence of the MPS I (Hurler, Hurler/Scheie and Scheie forms), MPS III (Sanfilippo) and MPS IVA (Morquio) was estimated at 0.63, 0.7 and 0.45 for 100,000 lives births respectively .
MPS I is the most common mucopolysaccharidosis worldwide, with an average incidence of about 1.7 in 100.000 live births for the severe and mild forms . The incidence of MPS I in Tunisia is also high, estimated at 0.63 in 100.000 live births , explained by the high rate of consanguinity.
Indeed, Tunisian population is characterized by the large family size, high maternal and paternal age  and a particularity high level of inbreeding with consanguinity rates in the range of 32-60% (all disconcerted degree), according to a traditional practice followed the same tribe, will age or social unit . These high consanguinity rates lead to the emergence of autosomal recessive disease at high frequencies; L Romdhane and al. described 346 genetics disorders identified in Tunisian population. Among these, 62.9% are autosomal recessive in which MPS I are included  also in Moroccan population .
In fact, all affected patients studied here are offspring of consanguineous marriages between first degree cousins in families 2, 4, 5, 6, C, D and E, second cousins in families 3, 7, 8, B and F and third cousins twice removed in families 1 and A (Table 1). This social fact may explain the high frequency of MPS I detection in Tunisian population.
Our molecular study [8, 10–12] covering the period 2004 - 2011 showed that the most common MPS I mutation in our country are P533R which represent 53.57% of all mutated MPS I alleles found in this cases study. These data are consistent with the previous Tunisian study where three novel mutations were found [11, 12]. Tunisia has different MPS I mutations frequencies (Table 2) compared to those of other European countries. We found that 53.57% (15/28) mutated alleles carried the p.P533R mutation, 52.57% of them in a homozygosity status and 1% in a heterozygosity status. Such a high prevalence of this mutation has already been described in the Maghrebian population such as in Morocco (92%) in Tunisia and also in the Maghrebian immigrant population in France [13, 14]. In Europe, this mutation has only been found among Italian patients with the frequency of 11% .
We actually discovered that the three affected families (families 3, B and F) have a parental relationship (Figure 1), suggesting that these families possibly originated from a common ancestor. Both traditional and social concerns such as geographical proximities, similar instruction level, lead the couples to behave in a collective model, whatever conscious degree they have about the consequences.
The mucopolysaccharidoses such as MPS I and IVA have been frequently reported in studies from all over the world such as in Japan and Australia; however the impact of inbreeding in the incidence of these types of disorders has not been described despite of the important rate of consanguinity in some isolated communities such as in Hirado in Japan (14.7%)  or in immigrant ethnic groups, e.g., Lebanese in Australia (35.8%) . An association between consanguinity and the MPS I and IVA, especially in Tunisia, is suggested according to general consanguineous data in addition to our specific Tunisian experience in MPS I and MPS IVA (pedigrees, inbreeding coefficients) .
It should be noted that there is a close relationship between inbreeding and not only concerning the high incidence of certain molecular lesions and their founder effect but also the appearance of new mutations e.g., p.F177S, p.L530fs and p.L578Q.
Associations between a specific mutation and a specific haplotype has been already demonstrated in genetic disorders  and revealed that the specific mutation was on a common background which suggests that these mutant alleles were "identical by descent" and were derived from a common ancestor.
Furthermore, the Tunisian population is also characterized by its heterogeneity in its genetic structure resulting from the mixing with other human groups from the history by invasions and migrations . A large spectrum of mutations leading to some disorders such as hemoglobinopathies especially beta-thalassemia is identified as a result of rare alleles selection .
In fact, inbreeding increases the frequency of homozygotes in the population and hence the risk of suffering morbid. According to several studies, this behavior appears to be closely linked to socio-economic and cultural populations. Arab-Muslim populations are more affected by this practice than others. In Arab societies, all categories of cousins are getting married [2, 13, 14, 16]. Studies of Arab and Islamic families show that inbreeding is still a common feature of the system of alliances still contracted in many countries i.e. Jordonia, Palestine, Syria, Iraq, Kuwait, Saudi Arabia, Kurdistan, Iran, Pakistan, Egypt, Sudan, North Africa (e.g. Tunisia) and Lebanon [19–21].
MPS present a social and economic impact at familial and also national level since these diseases (all types taken together and also MPS I separately) are still not rare in our area and there is no effective therapeutic means, until now. This situation justifies the need and importance of prenatal diagnosis. Two families (1 and E) received a prenatal diagnosis  and one patient (family F) had given bone marrow transplantation with succeed.