Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

Abstract

The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and the major factors that influence the results of biochemical analysis. Compared to regular biochemical testing, this is a complex process carried out by a medical physician specialist. It is comprised of an integrated program requiring multidisciplinary approach such as, pediatric specialist, expert scientist, clinical laboratory technician, and nutritionist. Tandem mass spectrometry is a powerful tool to improve screening of newborns for diverse metabolic diseases. It is likely to be used to analyze other treatable disorders or significantly improve existing newborn tests to allow broad scale and precise testing. This new era of various screening programs, new treatments, and the availability of detection technology will prove to be beneficial for the future generations.

Differential mobility spectrometry (DMS) reveals the elevation of urinary acetylcarnitine in non‐human primates (NHPs) exposed to radiation

“…LC‐MS/MS and GC‐MS coupled to tandem mass spectrometry are currently the accepted methods for acylcarnitine profiling in a variety of applications including newborn screening . However, the incorporation of DMS on the front end of a mass spectrometer provides an additional level of selectivity, leading to a high‐throughput technique for the quantitation of acetylcarnitine.…”

“…LC-MS/MS and GC-MS coupled to tandem mass spectrometry are currently the accepted methods for acylcarnitine profiling in a variety of applications including newborn screening. 4,6,7 However, the incorporation of DMS on the front end of a mass spectrometer provides an additional level of selectivity, leading to a high-throughput technique for the quantitation of acetylcarnitine. It is important to note that the reported sample preparation method is somewhat laborious and time-consuming; however, the SPE step can certainly be automated through the use of liquid handling devices.…”

“…Because the role of fatty acid and glucose oxidation in the pathogenesis of Type 2 Diabetes Mellitus is unclear, specific markers of oxidation, such as acylcarnitines, are often quantitatively assessed. In addition, acylcarnitine profiling is routinely performed during newborn screening in order to diagnose particular metabolic disorders . In this context, accurate and precise measurements of acylcarnitines are critical in understanding the progression of several disease states, including more than 20 fatty acid disorders …”

“…In addition, acylcarnitine profiling is routinely performed during newborn screening in order to diagnose particular metabolic disorders. 4 In this context, accurate and precise measurements of acylcarnitines are critical in understanding the progression of several disease states, including more than 20 fatty acid disorders. 5 Historically, acylcarnitines have been measured by gas chromatography-mass spectrometry (GC-MS), 6 or liquid chromatography-tandem mass spectrometry (LC-MS/MS).…”

Peculiarites of Metabolic Profiles of Amino Acids and Acylcarnitines in Dry Blood Spots of Children with Seizures

“…Однак у ході такого скринінгу в пацієнтів із судомами виявляють як специфічні зміни метаболітів при СПМ, так і вторинні метаболічні зміни, що часто дуже подібні на зміни метаболітів при СПМ. Такі вторинні зміни можуть бути спричинені віком пацієнта, часом забору матеріалу, вживанням певних лікарських засобів і фізіологічним станом [5]. Щоб уникнути хибної інтерпретації результатів, необхідно враховувати наведені вище фактори та використовувати критерії диференціації первинних і вторинних змін метаболітів у крові.…”