Hepatic Carnitine Palmitoyltransferase I Deficiency: Acylcarnitine Profiles in Blood Spots Are Highly Specific

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 CP...

Full description

Saved in:
Bibliographic Details
Published in:Clinical chemistry (Baltimore, Md.) Md.), 2001-10, Vol.47 (10), p.1763-1768
Main Authors: Fingerhut, Ralph, Roschinger, Wulf, Muntau, Ania C, Dame, Torsten, Kreischer, Jens, Arnecke, Ralf, Superti-Furga, Andrea, Troxler, Heinz, Liebl, Bernhard, Olgemoller, Bernhard, Roscher, Adelbert A
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomarkers - blood
Blood Specimen Collection
Carnitine - analogs & derivatives
Carnitine - blood
Carnitine O-Palmitoyltransferase - deficiency
Errors of metabolism
Humans
Infant
Infant, Newborn
Investigative techniques, diagnostic techniques (general aspects)
Liver - enzymology
Male
Medical sciences
Metabolic diseases
Neonatal Screening
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Proteins and glycoproteins
Sensitivity and Specificity
Spectrometry, Mass, Electrospray Ionization
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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). 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. 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]. 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.
ISSN:0009-9147
1530-8561
DOI:10.1093/clinchem/47.10.1763