Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles

Heiner-Fokkema, M. R., Vaz, F. M., Maatman, R., Kluijtmans, L. A. J., Spronsen, van, F. & Reijngoud, D-J., 14-Jun-2016, JIMD Reports. Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J. & Peters, V. (eds.). Springer Berlin Heidelberg, Vol. 32. p. 33-39 7 p. (JIMD Reports; vol. 32).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademic

BACKGROUND: Carnitine palmitoyltransferase IA (CPT-IA) deficiency is an inherited disorder of the carnitine cycle (MIM #255120). Patients affected by this deficiency might be missed easily because of lack of specific and sensitive biochemical markers. In this study, sensitivity and specificity of plasma free carnitine (C0) and long-chain acylcarnitines (lc-ac: C16:0-, C16:1-, C18:0-, C18:1- and C18:2-ac) was evaluated, including the sum of lc-ac (∑lc-ac) and the molar ratios C0/(C16:0-ac+C18:0-ac) and C0/∑lc-ac.

METHODS: Nine plasma acylcarnitine profiles of 4 CPT-IA deficient patients were compared with profiles of 2,190 subjects suspected of or diagnosed with an inherited disorder of metabolism. Age-dependent reference values were calculated based on the patient population without a definite diagnosis of an inborn error of metabolism (n = 1,600). Sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves were calculated based on samples of the whole patient population.

RESULTS: Concentrations of C0 in plasma were normal in all CPT-IA deficient patient samples. ROC analyses showed highest diagnostic values for C18:0-ac, C18:1-ac, and ∑lc-ac (AUC 1.000) and lowest for C0 (AUC 0.738). Combining two markers, i.e., a plasma C18:1-ac concentration <0.05 μmol/L and a molar ratio of C0/(C16:0-ac+C18:0-ac) >587, specificity to diagnose CPT-IA deficiency increased to 99.3% compared with either C18:1-ac (97.4%) or C0/(C16:0-ac+C18:0-ac) (96.9%) alone, all at a sensitivity of 100%.

CONCLUSIONS: Combination of a low concentration of C18:1-ac with a high molar ratio of C0/(C16:0-ac+C18:0-ac) ratio in plasma has high diagnostic value for CPT-IA deficiency. Patients with a clinical suspicion of CPT-IA deficiency can be diagnosed with this test combination.

Original languageEnglish
Title of host publicationJIMD Reports
EditorsEva Morava, Matthias Baumgartner, Marc Patterson, Shamima Rahman, Johannes Zschocke, Verena Peters
PublisherSpringer Berlin Heidelberg
Number of pages7
ISBN (Electronic)978-3-662-54385-6
ISBN (Print)978-3-662-54384-9
Publication statusPublished - 14-Jun-2016

Publication series

NameJIMD Reports
PublisherSpringer Berlin Heidelberg
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

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