Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism

Abstract

Children with certain inherited metabolic disorders excrete diagnostic acylcarnitines which reflect unusual acyl-CoA intermediates accumulating at the metabolic block (Roe et at., 1986). These metabolites can be detected in urine, if their concentration exceeds about 50nmol/ml, by fast atom bombardment mass spectrometry (FAB-MS). By applying tandem mass spectrometry (MS/MS) it is possible to lower the detection limit to 1 nmot/ml in urine or blood (Millington et al., 1989). We investigated the potential of this new technique to identify metabolic disorders from small blood samples and from blood spots taken for existing neonatal screening tests (Guthrie cards). The preliminary results are presented here. These children were not receiving L-carnitine supplements at the time of sampling. A sample of umbilical cord blood from a normal child was employed as a control. The original Guthrie cards were recovered for children with subsequently confirmed diagnoses of MCAD deficiency and propionic acidaemia, recently diagnosed at Duke Medical Center. Controls were obtained from the North Carolina State laboratory. To determine recovery, normal blood was spiked appropriately with known concentrations of specific acylcarnitines and internal standards after spotting onto and recovery from Guthrie cards, as described by Millington et al. (1989). 321

Fatty Acid Oxidation Disorders in a Chinese Population in Taiwan

“…The mortality rate of FAO disorders was approximately 48% but could be higher in specific diseases such as VLCAD deficiency (60%) or CATC deficiency (92%) (Baruteau et al 2012). After the development of tandem mass spectrometry (MS/MS) analysis of acylcarnitines (Millington et al 1990), the number of disorders that could be detected by newborn screening greatly increased (Huang et al 2006), and most aminoacidopathies, FAO disorders, and organic acidurias became diagnosable. The combined incidence of FAO disorders reaches 1:9,000 in some countries, and half of the detected patients are affected by MCAD deficiency (Zytkovicz et al 2001;Lindner et al 2010).…”

Relevance of Expanded Neonatal Screening of Medium-Chain Acyl Co-A Dehydrogenase Deficiency: Outcome of a Decade in Galicia (Spain)

“…Correct dietary management avoids or minimizes the number of metabolic decompensation episodes. Therefore, early identification of MCADD deficient individuals is important and newborn screening (NBS) by tandem mass spectrometry (MS/MS) for MCADD (Millington et al 1990) has been initiated in numerous countries over the last decade. In Galicia (northwest Spain), NBS by MS/MS was started in July 2000.…”

Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease

“…Moreover, fasting studies are relatively time-consuming, expensive, invasive, and potentially dangerous. These fasting studies have merely been replaced after the introduction of new laboratory techniques, like acylcarnitine profiling (Millington et al 1990). More recently, next-generation sequencing and exome sequencing have developed into powerful diagnostic confirmatory tests (Wang et al 2012).…”