Background: In patients with fatty acid oxidation disorders (FAODs) and organic acidurias (OAs) "secondary carnitine deficiency" occurs. In OAs carnitine supplementation is widely performed and dose is often adjusted to blood-free carnitine levels. Dried blood spots (DBS) are mostly used to measure carnitine status, however measurements in plasma are discussed to be more accurate. The concentration and the predictive value of the carnitine precursor γ-butyrobetaine in blood during carnitine deficiency are unknown.
Methods: Free carnitine and γ-butyrobetaine were quantified by tandem mass spectrometry in plasma and DBS from supplemented patients with OAs (n=18) and unsupplemented patients with FAODs (n=66) and were compared with healthy controls (n=50).
Results: Carnitine concentrations in plasma were significantly higher than in DBS. In contrast, γ-butyrobetaine concentrations in plasma were significantly lower than in DBS. Supplemented patients had high free carnitine concentrations in combination with high γ-butyrobetaine concentrations. Unsupplemented carnitine palmitoyltransferase I-deficient patients had exceptionally high free carnitine concentrations without elevated γ-butyrobetaine, however, carnitine in plasma was much lower than in DBS. In patients with low carnitine, γ-butyrobetaine in plasma is no evidence of induced carnitine biosynthesis.
Conclusions: Parallel measurements in plasma and DBS demonstrated that numerous patients with low values in DBS had normal values when measured in plasma, suggesting plasma to be the more appropriate medium to use for carnitine status monitoring. In contrast, diagnosis of CPT-I deficiency may be missed when analysis is performed in plasma. Carnitine supplementation presumably inhibits γ-butyrobetaine dioxygenase and results in high γ-butyrobetaine.
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