Tandem Mass Spectrometry Newborn Screening for Inborn Errors of Intermediary Metabolism: Abnormal Profile Interpretation

Abstract

Expanded newborn screening for inherited metabolic disorders using tandem mass spectrometry was introduced in 1990's and is widely used around the world. In contrast to conventional screening methods, tandem mass spectrometry does not measure single analytes but identifies and quantifies metabolite profiles; one single blood spot analyzed provides information of about 60 metabolites including amino acids, acylcarnitines and related ratios that enable the diagnosis of approximately 50 different diseases. However, the interpretation of these profiles can become quite complex. The aim of this work is to present in an easy and practical manner a comprehensive compilation of information needed for tandem mass neonatal screening profile interpretation, and basic actions for immediate follow up of abnormal results, including the tests that are required for confirmatory purposes. Other conditions not attributable to metabolic disorders which can lead to an abnormal profile of these markers are also described as well as a series of general recommendations which would be useful for health professionals who are beginning newborn screening for inborn errors of intermediary metabolism using tandem mass spectrometry.

Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias

“…An example of diagnosis of pre- and a-symptomatic diseases is represented by the targeted metabolomic approach applied to newborn screening for inherited metabolic disorders. The IEMs including OAs were diagnosed by using tandem mass spectrometry since the 1990s [ 42 , 43 ]. More than 70 different metabolic diseases can be diagnosed by measuring metabolites extracted from a single dried blood spot (DBS) collected within 48–72 hours of birth.…”

Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy

“…Impaired acylcarnitines profile not only may be a consequence of inherited metabolic diseases (IMD), but also might be the reflection of different pathologies such as sepsis, malnutrition, type I and II diabetes, obesity, and intrauterine growth restriction. [1–6] This versatility is due to the fact that the free hydroxyl group of LC—a semi-essential nutrient for the newborn [7–9] —can react with a wide range of molecules resulting in a broad spectrum of molecule structures, and in its capability to transfer esterified metabolites. [10]…”

Clinical and laboratory analysis of late-onset glutaric aciduria type I (GA-I) in Uighur: A report of two cases

“…This results in an increase in urine levels of glutaric acid and 3-hydroxy-glutaric acid (1). It has been reported that the incidence rate of GA-I is ~1:100,000 (2). Approximately 90% of patients develop GA-I in early childhood, and the remaining 10% of patients show mild symptoms or no symptoms (3).…”