Hepatic carnitine palmitoyltransferase I deficiency: Acylcarnitine profiles in blood spots are highly specific

Background: In camitine palmitoyltransferase I (CPT-I) deficiency (MIM 2551 20), free carnitine can be increased with no pathologic acylcarnitine speci es detectable. As inclusion of CPT-l deficiency in high-risk and newborn sc reening could prevent potentially life-threatening complications, we tested whether CPT-I deficiency might be diagnosed by electrospray ionization-tan dem mass spectrometry (ESI-MS/MS). Methods: A 3.2-mm spot of whole blood dried on filter paper was extracted w ith 150 muL of methanol. After derivatization of carnitine and acylcarnitin es to their butyl esters, the samples were analyzed by ESI-MS/MS with 37.5 pmol Of L-[H-2(3)]carnitine and 7.5 pmol of L-[H-2(3)]palmitoylcarnitine as internal standards. Results: In all dried-blood specimens from each of three patients with CPT- I deficiency, we found an invariably increased ratio of free carnitine to t he sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)]. The ra tio in patients was between 175 and 2000, or 5- to 60-fold higher than the ratio for the 99.9th centile of the normal newborn population in Bavaria (n = 177 842). No overlap with the values of children that were known to be s upplemented with carnitine was detected [C0/ (C16 + C18), 34 +/- 30; mean /- SD; n = 27]. Conclusions: ESI-MS/MS provides a highly specific acylcarnitine profile fro m dried-blood samples. The ratio of free carnitine to the sum of palmitoylc arnitine and stearoylcarnitine [C0/(C16 + C18)] is highly specific for CPT- I deficiency and may allow presymptomatic diagnosis. (C) 2001 American Asso ciation for Clinical Chemistry.