Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene?

Mycobacteriosis in the compromised host

“…In the cases of children with the idiopathic disseminated BCG infection, a mendelian disorder of autosomal recessive inheritance was suggested by the high rates of affected siblings and parental consanguinity, together with the equal number of male and female children (Casanova et al 1996). The same observations were also reported in the Levin's study (Levin et al 1995). Moreover, the heterogeneity of clinical outcome and its correlation with the histopathological granulomatous type of the lesions, suggested that the underlying potential inherited disorder might be genetically heterogeneous (Jouanguy et al 1996).…”

“…By contrast with the well-known leading causes of disseminated disease in Aids patients, the MOTT and BCG vaccine have been shown also to cause severe disease in otherwise healthy children without any over immunodeficiency (Levin et al 1995, Casanova et al 1995, 1996. Unlike severe immunocompromised patients, being highly susceptible to a broad range of opportunistic pathogens, children with disseminated idiopathic BCG and MOTT infections do not have generally associated infections, apart from salmonellosis in less than half of the cases.…”

“…This was particularly true of the M. avium complex (MAC) because these organisms are the single most important cause of disseminated bacterial infection in Aids patients (Benson 1994). Third reason, a newly recognised pediatric syndrome, the idiopathic mycobacterial infection in non immuno-compromised children (Levin et al 1995), led to the identification of mendelian susceptibility to mycobacterial infection and several specific genetic deficiencies including receptors genes for important cytokines such as IFNγ and IL-12 (interleukin) have been described (Jouanguy et al 1999).…”

Susceptibility to mycobacterial infections: the importance of host genetics

“…In 1995, Levin and colleagues 77 described four children from the same village in Malta who had severe disseminated infections due to atypical mycobacteria (M. fortuitum, M. chelonae, M. avium-intracellulare). Three of the children came from the same consanguineous family, suggesting they had inherited the same genetic immune defect from a common ancestor.…”

Major histocompatibility complex and its importance towards controlling infection

“…[21][22][23][24][25][26][27] Other linkage studies to identify genes causing rare, monogenic susceptibility phenotypes have been reported, though the causative variation identified are rare mutations rather than polymorphisms and the identified genes rarely, if ever, relevant to common variation in susceptibility. 28,29 Thus, it is an area of intense interest that has been mainly focused on susceptibility to malaria, human immunodeficiency virus (HIV)/acquired immunodeficiency disease syndrome (AIDS) and mycobacterial infection; but other bacterial, viral and parasitic diseases are receiving increasing attention. The emerging picture is of highly polygenic diseases.…”