POPULATION SCREENING FOR THE COMMON G985 MUTATION CAUSING MEDIUM-CHAIN ACYL-COA DEHYDROGENASE-DEFICIENCY WITH EU-LABELED OLIGONUCLEOTIDES AND THE DELFIA SYSTEM

We have screened 10171 neonatal blood spots from the Trent and West Mi dlands regions of the UK for the common G985 mutation to more accurate ly establish the incidence of medium-chain acyl coenzyme (Co)A dehydro genase (MCAD) deficiency. We have used a technique involving PCR and E u-labeled allele-specific oligonucleotides detected by using time-reso lved fluorometry on the dissociation-enhanced fluorescence immunoassay (DELFIA) system for the detection of the G985 mutation. We have also evaluated the feasibility of neonatal screening with this technique. W e identified 158 G985 heterozygotes and no G985 homozygotes. The calcu lated incidence of MCAD deficiency in the population studied (all muta tions, assuming 90% of MCAD mutations are G985) is 1 in 13 426 (95% co nfidence limits 1 in 10 070-1 in 18 791). At the optimum cutoff criter ia, the technique has a sensitivity of 97.5%, specificity of 99.6%, an d positive predictive value of 80.2%. We conclude that this study conf irms that MCAD deficiency is a common inherited metabolic disease and is a candidate for neonatal screening. The methodology used is robust and suitable for large-scale population studies such as this. The tech nique is also potentially suitable for screening.