BACKGROUND: In carnitine palmitoyltransferase I (CPT-I) deficiency (MIM 255120), free carnitine can be increased with no pathologic acylcarnitine species detectable. As inclusion of CPT-I deficiency in high-risk and newborn screening could prevent potentially life-threatening complications, we tested whether CPT-I deficiency might be diagnosed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). METHODS: A 3.2-mm spot of whole blood dried on filter paper was extracted with 150 microL of methanol. After derivatization of carnitine and acylcarnitines to their butyl esters, the samples were analyzed by ESI-MS/MS with 37.5 pmol of L-[(2)H(3)]carnitine and 7.5 pmol of L-[(2)H(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 the sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)]. The ratio 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 supplemented with carnitine was detected [C0/(C16 + C18), 34 +/- 30; mean +/- SD; n = 27]. CONCLUSIONS: ESI-MS/MS provides a highly specific acylcarnitine profile from dried-blood samples. The ratio of free carnitine to the sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)] is highly specific for CPT-I deficiency and may allow presymptomatic diagnosis.
BACKGROUND: In carnitine palmitoyltransferase I (CPT-I) deficiency (MIM 255120), free carnitine can be increased with no pathologic acylcarnitine species detectable. As inclusion of CPT-I deficiency in high-risk and newborn screening could prevent potentially life-threatening complications, we tested whether CPT-I deficiency might be diagnosed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). METHODS: A 3.2-mm spot of whole blood dried on filter paper was extracted with 150 microL of methanol. After derivatization of carnitine and acylcarnitines to their butyl esters, the samples were analyzed by ESI-MS/MS with 37.5 pmol of L-[(2)H(3)]carnitine and 7.5 pmol of L-[(2)H(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 the sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)]. The ratio 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 supplemented with carnitine was detected [C0/(C16 + C18), 34 +/- 30; mean +/- SD; n = 27]. CONCLUSIONS: ESI-MS/MS provides a highly specific acylcarnitine profile from dried-blood samples. The ratio of free carnitine to the sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)] is highly specific for CPT-I deficiency and may allow presymptomatic diagnosis.
Authors: Regina Ensenauer; Ralph Fingerhut; Sonja C Schriever; Barbara Fink; Marc Becker; Nina C Sellerer; Philipp Pagel; Andreas Kirschner; Torsten Dame; Bernhard Olgemöller; Wulf Röschinger; Adelbert A Roscher Journal: J Lipid Res Date: 2012-02-16 Impact factor: 5.922
Authors: Ralph Fingerhut; Gabriel De Jesus Silva Arevalo; Matthias R Baumgartner; Johannes Häberle; Marianne Rohrbach; Andrés Weinfeld Ávalos Figueroa; Elena María Dardón Fresse; Olga Leticia Polanco; Toni Torresani Journal: J Inherit Metab Dis Date: 2010-07-21 Impact factor: 4.982
Authors: M Bellusci; P Quijada-Fraile; D Barrio-Carreras; E Martin-Hernandez; M Garcia-Silva; B Merinero; B Perez; A Hernandez-Lain Journal: J Inherit Metab Dis Date: 2017-05-02 Impact factor: 4.982
Authors: Melanie B Gillingham; Matthew Hirschfeld; Sarah Lowe; Dietrich Matern; James Shoemaker; William E Lambert; David M Koeller Journal: Mol Genet Metab Date: 2011-06-28 Impact factor: 4.797
Authors: Judith Simcox; Gisela Geoghegan; John Alan Maschek; Claire L Bensard; Marzia Pasquali; Ren Miao; Sanghoon Lee; Lei Jiang; Ian Huck; Erin E Kershaw; Anthony J Donato; Udayan Apte; Nicola Longo; Jared Rutter; Renate Schreiber; Rudolf Zechner; James Cox; Claudio J Villanueva Journal: Cell Metab Date: 2017-09-05 Impact factor: 27.287
Authors: Jong Sub Choi; Hyeoh Won Yoo; Kyung Jae Lee; Jung Min Ko; Jin Soo Moon; Jae Sung Ko Journal: Pediatr Gastroenterol Hepatol Nutr Date: 2016-03-22