Progressive encephalopathy (PE) in children is a heterogeneous group of individually rare diseases with a cumulative incidence which compares to that of neural tube defects and infantile hydrocephalus. The main cause of PE is metabolic disease, but neurodegenerative disorders lacking known metabolic or other causes also exist. PE poses a challenge to our health care system due to difficulties in its diagnosis and management, 4–6 and a high case fatality. For example, in a cohort study we showed that the case fatality of PE was 36.9%. In the same cohort, the incidence rate was 6.4 per 100,000 person years at risk, and the cumulative incidence was 0.6 per 1000 live births, comparable to that of other reports.
Using data from this cohort combined with outstandingly detailed national-wide population statistics we wanted to pin point the increased risk of PE associated with consanguinity. Over the past 20 years there has been a six-fold increase in non-Western immigration to Norway (the nomenclature regarding non-Western has recently been suggested revised). In 2006, non-Western immigrants accounted for 18.6% of Oslo’s total population of 538,411 inhabitants. The largest non-Western group is from Pakistan. In Pakistan, approximately 60% of marriages are consanguineous and unions occur primarily between first cousins. Norway is the only country in the world collecting data on consanguinity for its entire population at birth. Approximately 50% of children of Pakistani origin born in Norway are the result of consanguineous unions, defined as parents who are second cousins or more closely related. Of first generation Pakistani immigrants, 43.9% were first cousins. In Norway, parental consanguinity in the Pakistani population is associated with an increased risk of stillbirth, congenital malformations, and infant death, all considered complex genetic conditions.
When autosomal recessive gene defects are rare, the likelihood of unrelated parents being carriers for the same defect is small. The less frequent the recessive gene, the stronger the likelihood that an affected individual is the product of a consanguineous mating. Since many of the diseases causing PE are determined by single mutant genes, for example in autosomal recessive inborn errors of metabolism, it was reasonable to assume that children of consanguineous unions had a higher risk of PE, and that PE consequently would be more common in children of Pakistani origin. However, the degree of increased risk of PE caused by consanguinity has not been precisely assessed in previous studies. Here we report an approximately seven-fold increased risk of PE in children of Pakistani origin and an eleven-fold increased risk when consanguineous Pakistanis were compared to the general Norwegian population. We also estimated that avoidance of consanguinity in the Pakistani population would result in 50% reduction of PE in this group.
Saturday, June 09, 2012
Pakistani immigration to Norway increasing the incidence of progressive encephalopathy
Here's a recent study from The European Journal of Paediatric Neurology: