SCREENING FOR MEDIUM-CHAIN ACYL-COA DEHYDROGENASE-DEFICIENCY USING ELECTROSPRAY-IONIZATION TANDEM MASS-SPECTROMETRY

Objective-To establish criteria for the diagnosis of medium chain acyl -CoA dehydrogenase (MCAD) deficiency in the UK population using a meth od in which carnitine species eluted from blood spots are butylated an d analysed by electrospray ionisation tandem mass spectrometry (ESI-MS /MS). Design-Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A9 85G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. Results-All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 mu M and no accumulation of carnitine species > C-10 or < C-6. Among the patients with MCAD deficiency, the [C-8-Cn] was si gnificantly lower in children > 10 weeks old and in children with carn itine depletion (free carnitine < 20 mu M). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 mu M, whereas in het erozygotes and other normal neonates the [C8-Cn] was < 1.0 mu M. In co ntrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD defic iency > 10 weeks old fell within the same range as five of 15 MCAD het erozygotes (0.38-1.0 mu M). However, the free carnitine concentrations were reduced (< 20 mu M) in the patients with MCAD deficiency brat no rmal in the heterozygotes. Conclusions-Criteria for the diagnosis of M CAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of fals e positive and negative results should be negligible. Because there ha ve been no instances of death or neurological damage following diagnos is of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.