Potentials and pitfalls in neonatal screening for type 1 diabetes.
Childhood-onset diabetes is increasing all over the western world. Only 20-30% of monozygotic twin pairs are concordant for the disease. So far, more than 20 different risk genes have been identified on different chromosomes. The dominating risk genes differ with different age at onset and also in different populations. Thus, the aetiology of the disease is complex, with interactions between different risk genes and environmental risk factors. Several pathogenetic models have been proposed, most of which include autoimmune destruction mechanisms. Screening for genetic markers for diseases with such complex aetiology encounters pitfalls due to the low predictive value of each single marker in the general population. To overcome such problems combinations of markers and decision-tree analysis are necessary. The identification of several immune markers for the disease has provided potential for screening for secondary prevention. When increasing the number of markers to increase the predictive value, sensitivity will be lost. A Swedish population-based study found the best combined positive predictive value in the general population to be 20%, whereas the sensitivity was only 34%. Type 1 diabetes still needs more precise risk markers in addition to a very safe prevention strategy before neonatal screening programmes may be instituted.
Dahlquist
G
G
Department of Clinical Science, Umeå University, Sweden. gisela.dahlquist@pediatri.umu.se
D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000592:standards* / Q000639:trends; D011237:Predictive Value of Tests; D011322:Primary Prevention; D012680:Sensitivity and Specificity; D013548:Sweden
D005819:Genetic Markers