Reference values of amino acids, acylcarnitines and succinylacetone by tandem mass spectrometry for use in newborn screening in southwest Colombia

Abstract

Introduction: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput.Aims: Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM.Methods: Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. Results: fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. Conclusion: The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.

Age-Specific Cut-off Values of Amino Acids and Acylcarnitines for Diagnosis of Inborn Errors of Metabolism Using Liquid Chromatography Tandem Mass Spectrometry

“…This study is an initiative to overcome those issues, as here, we have demonstrated the establishment of cut-off values for different amino acids and acylcarnitines for 3 different age groups. Sex-dependent variations of blood amino acids and acylcarnitines concentrations are very rare and this is why we generated only age-specific data considering age-specific variations of blood metabolites in healthy population are frequently reported [7, 17, 18, 40]. Moreover, the cut-off limits for screening of some amino acids and acylcarnitines are very close to normal reference intervals [18].…”

“…Till date, about 1000 IEMs disorders have been identified [7]. However, the clinical manifestations of these disorders are often nonspecific and sometimes the signs and symptoms of an individual IEM overlap with other IEMs and even non-IEMs diseases, such as septicemia [2, 8, 9].…”

Dried Blood Spot in Laboratory: Directions and Prospects

“…DBS is also used to detect lysosomal diseases in newborns by measuring lysosomal enzymatic activity [74] Céspedes N. et al demonstrated a method for the simultaneous assessment of 57 analytes (amino acids, acylcarnitines and succinylacetone) associated with more than 40 congenital metabolic errors using tandem mass spectrometry (MS/MS). The analysis of DBS samples enriched with analyte and subsequently mixed with labeled internal standards (isotopic dilution method) showed a linear relationship between the data at a wide range of concentrations, with high sensitivity [75].…”

Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years’ experience from a reference center

“…Recently, some private institutions are performing screening tests for diagnose amino acids and organic acidurias through tandem mass spectrometry. Nevertheless, these diagnostics analyzes are carried out selectively, which limits the generation of relevant epidemiological data [ 19 , 20 ]. In the case of small molecule disorders (i.e.…”

“…Although significant improvements have been done during the last years in the diagnosis, treatment and follow up of these disorders in Colombia, future efforts should be focus in the decentralization and consolidation of specialized centers, as well as in the construction of knowledge networks, since until now the work in the field has focused on consolidation of individualized centers. In addition, we need to work in the empowerment of different patient advocacy groups, working together to achieve important goals such as the extended newborn screening program [ 32 , 99 ], the transition to new omics technologies [ 100 ], and the establishment of research programs sponsored by the government.…”