Elevations of C14:1 and C14:2 Plasma Acylcarnitines in Fasted Children: A Diagnostic Dilemma

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• 作者：Lindsay C. Burrage ; MD ; PhD¹ ; ² ; Marcus J. Miller ; PhD¹ ; Lee-Jun Wong ; PhD¹ ; Adam D. Kennedy ; PhD³ ; V. Reid Sutton ; MD¹ ; ² ; Qin Sun ; PhD¹ ; Sarah H. Elsea ; PhD¹ ; Brett H. Graham ; MD ; PhD¹ ; ² ; ^{bgraham@bcm.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NBS ; Newborn screening ; VLCAD ; Very long-chain acyl-CoA dehydrogenase
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：169
• 期：Complete
• 页码：208-213.e2
• 全文大小：1210 K

文摘

To test whether follow-up testing for very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency uncovers a diagnosis in patients with elevations of C14:1 and C14:2 plasma acylcarnitines after a controlled fasting study performed for clinically suspected hypoglycemia and to compare the acylcarnitine profiles from fasted patients without VLCAD deficiency vs patients with known VLCAD deficiency to determine whether metabolite testing distinguishes these groups.

Study design

We performed a retrospective chart review and identified 17 patients with elevated C14:1 and C14:2 plasma acylcarnitine levels after a controlled fast and with testing for VLCAD deficiency (ACADVL sequencing or fibroblast fatty acid oxidation studies). The follow-up testing in all patients was inconsistent with a diagnosis of VLCAD deficiency. We compared the plasma acylcarnitine profiles from these fasted patients vs patients with VLCAD deficiency.

Results

C14:1/C12:1 was significantly lower (P < .001) in fasted patients vs patients with VLCAD deficiency. Metabolomics analysis performed in 2 fasted patients and 1 patient with VLCAD deficiency demonstrated evidence for up-regulated lipolysis and β-oxidation in the fasted state.

Conclusions

Elevations of plasma C14:1 and C14:2 acylcarnitines appear to be a physiologic result of lipolysis that occurs with fasting. Both metabolomics analysis and/or C14:1/C12:1 may distinguish C14:1 elevations from physiologic fasting-induced lipolysis vs VLCAD deficiency.