Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles.
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.
Department of Laboratory Medicine, Laboratory of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Room Y2.125, HPA EA60, 30.001, NL-9700 RB, Groningen, The Netherlands. m.r.heiner@umcg.nl.
M Rebecca
MR
Heiner-Fokkema
Department of Clinical Chemistry and Pediatrics, Laboratory of Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Frédéric M
FM
Vaz
Medlon BV, Enschede, The Netherlands.
Ronald
R
Maatman
Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Leo A J
LA
Kluijtmans
Division of Metabolic Diseases, University Medical Center Groningen, University of Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
Francjan J
FJ
van Spronsen
Department of Laboratory Medicine, Laboratory of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Room Y2.125, HPA EA60, 30.001, NL-9700 RB, Groningen, The Netherlands.
Dirk-Jan
DJ
Reijngoud
Acylcarnitines; Carnitine palmitoyltransferase type IA deficiency; Free carnitine; Plasma; Sensitivity; Specificity