RAPID DIAGNOSIS OF MCAD DEFICIENCY - QUANTITATIVE-ANALYSIS OF OCTANOYLCARNITINE AND OTHER ACYLCARNITINES IN NEWBORN BLOOD SPOTS BY TANDEM MASS-SPECTROMETRY

We report the application of tandem mass spectrometry to prospective n ewborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) defici ency. MCAD deficiency is diagnosed from dried blood spots on filter pa per cards from newborns on the basis of the increase of medium chain l ength acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis o f medium chain length acylcarnitines as their butyl esters was develop ed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low co ncentrations of medium chain length acylcarnitines such as octanoylcar nitine. The maximum concentration of octanoylcarnitine was 0.22 mu mol /L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcar nitine was highly increased [median 8.4 mu mol/L (range 3.1-28.3 mu mo l/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than i n 16 older patients (ages 8 days to 7 years) with MCAD deficiency (med ian 1.57 mu mol/L, range 0.33-4.4). The combined experience of prospec tive newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positiv e and no known false-negative results have been found. A validated met hod now exists for prospective newborn screening for MCAD deficiency.