3-Hydroxyisovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase deficiency.
A new acylcarnitine was observed in the plasma and urine of a patient with isolated 3-methylcrotonyl-CoA carboxylase deficiency. Analysis by tandem mass spectrometry of the methyl ester and butyl ester and their fragment ion spectra identified it as a 3-hydroxy-C5-acylcarnitine. Fibroblasts from a second patient were incubated with deuterium-labelled leucine. Incorporation of label in the new acylcarnitine identified its origin from leucine, and thus confirmed the structure as 3-hydroxyisovalerylcarnitine. The presence of elevated amounts of this metabolite, plus a small amount of 3-methylcrotonylcarnitine in plasma, was diagnostic for isolated 3-methylcrotonyl-CoA carboxylase deficiency. Other conditions in which a hydroxy-C5-acylcarnitine was present were readily differentiated by the abnormal elevation of other acylcarnitines.
van Hove
J L
JL
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
Rutledge
S L
SL
Nada
M A
MA
Kahler
S G
SG
Millington
D S
DS
D019735:Carbon-Carbon Ligases; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D003903:Deuterium; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007930:Leucine / Q000378:metabolism; D008025:Ligases / Q000172:deficiency*; D013058:Mass Spectrometry
C098116:3-hydroxyisovalerylcarnitine; D003903:Deuterium; D008025:Ligases; D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase; D007930:Leucine; D002331:Carnitine