Acylcarnitines in intermediary metabolism

Sewell, A. C.; Böhles, H.

doi:10.1007/bf01957495

Cited by 36 publications

(31 citation statements)

References 44 publications

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“…Although this reference value does not take into consideration fluctuations related to feeding or fasting states, it is considered abnormal when the ratio is Ͼ0.4, indicating accumulation of AC and/or reduced FC. This ratio is often abnormal in inborn errors of metabolism such as fatty acid oxidation deficiencies, other mitochondrial disorders, and organic acidurias (1,13,14). The high AC/FC ratio noted in neonates is thought to reflect the increased production of acyl-CoA derivatives, mainly acetylCoA, produced by the normally enhanced fatty acid oxidation in the newborn period (3,5,6,19,26) when the neonate is first exposed to fasting.…”

Section: Discussionmentioning

confidence: 99%

“…Reduction of FC and accumulation of AC is a common feature of inborn errors of metabolism affecting fatty acid oxidation and other mitochondrial disorders (1,13,14). These diseases often present in the neonatal period and early infancy (1).…”

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confidence: 99%

“…The sum of free carnitine (FC) and acylcarnitine (AC) equals total carnitine (TC). The fraction of esterified carnitine varies depending on the tissue and on the metabolic status (1,13,14).…”

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confidence: 99%

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Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry

Chace¹,

Pons

Chiriboga

et al. 2003

Pediatr Res

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Despite a number of published reports, there is limited information about carnitine metabolism in the newborn. To establish normative data, we analyzed whole-blood carnitine concentrations in 24,644 newborns at age 1.85 Ϯ 0.95 d and umbilical cord whole blood and plasma carnitine concentrations in 50 full-term newborns. Total carnitine (TC), free carnitine (FC), and acylcarnitine (AC) were measured by electrospray tandem mass spectrometry. AC/FC ratios were derived from these measurements. The entire cohort was stratified according to TC values into a middle TC group representing 90% of the population and lower and upper TC groups representing 5% of the population, respectively. Normative data were derived from the middle TC group of full-term infants (N ϭ 19,595). TC was 72.42 Ϯ 20.75 M, FC was 44.94 Ϯ 14.99 M, AC was 27.48 Ϯ 8.05 M, and AC/FC ratio was 0.64 Ϯ 0.19 (ϮSD). These values differed significantly from umbilical cord whole blood TC values of 31.27 Ϯ 10.54 M determined in 50 samples. No meaningful correlation was found between TC and gestational age or birth weight in any group. In controlled analyses, prematurity was not associated with TC levels, whereas low birth weight (Ͻ2500 g) and male sex were significantly associated with higher TC levels. The association of low birth weight with higher TC values may be related to decreased tissue carnitine uptake. The sex effect may be related to hormonal influences on carnitine metabolism. Our study provides normative data of carnitine values measured by the highly precise method of electrospray tandem mass spectrometry in a large cohort of newborns and provides the basis for future studies of carnitine metabolism in health and disease states during the neonatal period. Abbreviations MS-MS, electrospray tandem mass spectrometry TC, total carnitine FC, free carnitine AC, acylcarnitine RBC, red blood cells OR, Odds ratio CI, 95% confidence interval RE, radioenzyme L-Carnitine serves as a carrier for acyl groups across the mitochondrial membrane. It is essential for the membrane transport and subsequent intramitochondrial ␤-oxidation of long-chain fatty acids and for the modulation of CoA homeostasis (1, 2). Adequate tissue levels of carnitine are crucial in the neonatal period, because mitochondrial oxidation of fatty acids is essential for the production of energy in newborns (3-6).L-Carnitine is derived mainly from exogenous sources and in part from endogenous synthesis (1). The main source of carnitine in the fetus seems to be transplacental transfer (4,7,8) and in the newborn seems to be breast milk or carnitine-supplemented formulas (3, 9 -11). Endogenous synthesis plays a minor role in early life because the activity of ␥-butyrobetaine hydroxylase, the enzyme necessary for carnitine synthesis, is very low (12).In tissues and body fluids, carnitine is present in free and esterified forms. The sum of free carnitine (FC) and acylcarnitine (AC) equals total carnitine (TC). The fraction of esterified carnitine varies depending on the tissue and on the metaboli...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry

Chace¹,

Pons

Chiriboga

et al. 2003

Pediatr Res

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“…14 Beyond being biomarkers of FAO dysfunction and compromised energy metabolism, acylcarnitines themselves are thought to be cytotoxic, particularly to myocytes and hepatocytes. 15,16 To date little is known about the effects of HIV or ARV on fatty acid and acylcarnitine metabolism in neonates, although we recently reported a higher proportion of abnormal ACP in HIV-exposed infants compared to the general population of newborns. 17 In this study we sought to determine the prevalence of abnormal ACP in a large cohort of HIV-exposed, uninfected (HEU) newborns and explore the association of abnormal ACP with clinical laboratory outcomes and in utero ARV exposures.…”

Section: Introductionmentioning

confidence: 96%

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Kirmse

Yao

Hofherr

et al. 2016

AIDS Research and Human Retroviruses

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We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PIcontaining as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.

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“…When acylCoAs accumulate in the mitochondrial matrix due to a specific metabolic disease, AC formation is favored, and then accumulation of AC in all physiological fluids reflects the mitochondrial acyl-CoA status. Consequently, the analysis of AC provides indirect evidence of mitochondrial metabolism (Bohles et al 1994;Sewell and Bohles 1995).…”

Section: Introductionmentioning

confidence: 99%

Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum

Ruíz-Sala¹,

Ruijter²,

Acquaviva³

et al. 2016

JIMD Reports

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The analysis of acylcarnitines (AC) in plasma/ serum is established as a useful test for the biochemical diagnosis and the monitoring of treatment of organic acidurias and fatty acid oxidation defects. External quality assurance (EQA) for qualitative and quantitative AC is offered by ERNDIM and CDC in dried blood spots but not in plasma/serum samples. A pilot interlaboratory comparison between 14 European laboratories was performed over 3 years using serum/plasma samples from patients with an established diagnosis of an organic aciduria or fatty acid oxidation defect. Twenty-three different samples with a short clinical description were circulated. Participants were asked to specify the method used to analyze diagnostic AC, to give quantitative data for diagnostic AC with the corresponding reference values, possible diagnosis, and advice for further investigations.Although the reference and pathological concentrations of AC varied among laboratories, elevated marker AC for propionic acidemia, isovaleric acidemia,

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Acylcarnitines in intermediary metabolism

Cited by 36 publications

References 44 publications

Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry

Neonatal Blood Carnitine Concentrations: Normative Data by Electrospray Tandem Mass Spectometry

Acylcarnitine Profiles in HIV-Exposed, Uninfected Neonates in the United States

Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum

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