Metabolic Diseases and Newborn Screening

Title Summary Year
Heterogenous Clinical Landscape in a Consanguineous Malonic Aciduria Family With the introduction of malonyl-CoA decarboxylase deficiency in newborn screening programs, the number of patients is expected to rise, according to the small study. Acylcarnitines measured with Chromsystems assay. 2021
Acylcarnitines’ Level in the Dried Blood Spot Samples of Healthy Newborns in Serbia-The Pilot Study The distribution of the ACs levels, measured using tan-dem mass spectrometry, in DBS from healthy newborns in the Republic of Serbia substantially matches the worldwide estimates. Also, the established cut-off values were success-fully verified in comparison with the worldwide ranges and data from individual studies in several Caucasian popula-tions. Measured with MassChrom Amino Acids and Acylcarnitines assay. (derivatised) 2021
Extremely low birthweight neonates with phenylketonuria require special dietary management Extremely low birthweight neonates with PKU need special dietary management. Regular assessments of phenylalanine are necessary during the first weeks of life to allow prompt dietary adjustments that reflect rapid weight gain and transitory high tolerance to phenylalanine. Analysis with MassChrom Amino Acids and Acylcarnitines assay performed. 2021
Diagnostic et suivi de la phénylcétonurie par LC-MS-MS au Maroc Phenylketonuria is a disease that would be frequent in Morocco but it is still diagnosed at the stage of severe mental retardation. A better management of these patients could be considered when setting up a nation-wide neonatal screening program. Measured with Chromsystems Newborn Screening assay 2021
Treatment adherence in tyrosinemia type 1 patients Despite initially poor adherence to pharmacological and especially dietary treatment among HT1 patients, positive reinforcement at medical consultations resulted in a marked improvement in NTBC levels, indicating the importance of systematic positive reinforcement at medical visits. Measured with MassChrom NBS assay. 2021
A branched‐chain amino acid‐based metabolic score can predict liver fat in children and adolescents with severe obesity High levels of branched‐chain amino acids could be an important link between obesity and other metabolic pathways. Amino acids and acylcarnitines were measured with Chromsystems assay (non-derivatised). 2021
Liraglutide treatment and acylcarnitine profiles in Egyptian obese insulin-resistant females Liraglutide treatment leads to durable improvements in weight reduction and glycometabolic control and the utilization of intracellular glucose. Acylcarnitines was used with MassChrom Amino Acid Analysis assay (non-derivatised). 2021
Metabolic Serendipities of Expanded Newborn Screening This work describes four case reports that had incidental findings on the NBS, which eventually led to the diagnosis of another metabolic disease instead of the one that was initially suspected. MassChrom Amino Acids and Acylcarnitines was used. 2020

A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity
According to the study, plasma branched-chain amino acids (CAAA) could be an important link between obesity and other metabolic
pathways. The study used MassChrom Amino Acids and Acylcarinitines (non-derivatised).
Investigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia The study demonstrates that a combination of whole-exome sequencing (WES) and computational analysis are potent tools for validation of diagnosis and classification of disease-causing variants. MassChrom Amino Acids and Acylcarnitines was used. 2020
Postnatal induction of muscle fatty acid oxidation in mice differing in propensity to obesity: a role of pyruvate dehydrogenase The results indicate a relatively strong postnatal induction of FA oxidation in skeletal muscle of the obesity-resistant A/J mice. This induction is transient and probably results from suppression of PDH activity, linked with a postnatal surge in plasma leptin levels, independent of AMPK. AA and Acylcarnitines measured by MassChrom Amino Acids assay. 2020
Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases This assessment contributes to the identification of the unique metabolic features exhibited in association with cardiometabolic risk in adults diagnosed with CVD. The altered metabolites have the potential to be used as biomarkers for early detection of CVD. Measured with the NBS assay that was adopted to plasma determination. 2020
Analysis of Mucopolysaccharidosis Type VI throughIntegrative Functional Metabolomics The study's findings might shed light on molecular understanding of mcopolysaccharidoses pathophysiology to develop further studies to enhance diagnosis and treatments of this rare condition. MassChrom Amino Acids and Acylcarnitines was used.  2019
Clinical, biochemical, neuroradiological and molecular characterization of Egyptian patients with glutaric acidemia type 1 The authors concluded that glutaric acidemia type 1 disease is uncommon in Egypt and must be included in the comprehensive newborn screening practices in Egypt, which lacks a comprehensive program. MassChrom Amino Acids and Acylcarnitines was used.  2019
EPIDEMIOLOGY OF RARE DISEASES DETECTED BYNEWBORN SCREENING IN THE CZECH REPUBLIC Epidemological study in the Czech Republic that used MassChrom assay for screening on amino acids and acylcarnitines 2019
Novel Markers of the Metabolic Impact of Exogenous Retinoic Acid with A Focus on Acylcarnitines and Amino Acids The results connect all-trans retinoic acid to specific nutrition-modulated biochemical pathways, and suggest novel mechanisms of action of vitamin A-derived retinoic acid on metabolic health. Amino acids and acylcarnitines were measured with the MassChrom assay 2019
The evaluation of phenylalanine levels in Estonian phenylketonuria patients during eight years by electronic laboratory records Clinical study on phenylalanine levels of PKU patients using MassChrom Amino Acid Test 2019
An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia MassChrom Amino Acid Test was used to investiagte the prevalence of SCADD in the slovakian population 2018
Neonatal screening in the Czech Republic: increased prevalence of selected diseases in low birthweight neonates The Chromsystems assays have been used to determine an increased prevalence of diseases in low weight babies 2018
An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia Based on the exceeded levels of the specific biomarker C4-acylcarnitine as well as ethylmalonic acid, we revealed a high prevalence of short-chain acyl-CoA dehydrogenase deficiency cases, confirmed by the findings of two rare pathogenic variants. Acylcarnitines were measured with MassChrom Amino Acids and Acylcarnitines assay.  2018
Plasma free amino acid profile changes in hepatocellular carcinoma patients MassChrom Amino Acids and Acylcarnitines in DBS (non-derivatised) was used to determine an amino acid profile in cancer patients.  2016
Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice Results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity. MassChrom Amino Acids and Acylcarnitines was used.  2016
A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD) The Chromsystems assay was used for investigating a SCADD patient and discovered an increase in some specific acylcarnitines.  2015
Selective Screening for Metabolic Disorders in the Slovenian Pediatric Population MassChrom Amino Acids and Acylcarnitines was used in a Slovenian study  2014
Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs SUAC measurements may improve Tyr I false positive and false-negative results 2014
screening programme in Slovenia. Newborn screening performed with MassChrom Amino Acids and Acylcarnitines. 
Selective newborn screening of inborn errors of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain The study, conducted with MassChrom Amino Acids from DBS, recommends mandatory screening for inborn errors of metabolism in Bahrain. 2013


Title Summary Year
Differences of Phenylalanine Concentrations in Dried Blood Spots and in Plasma: Erythrocytes as a Neglected Component for This Observation Variances of Phe concentrations in plasma and DBS are not linear but increases with higher concentrations indicating heteroscedasticity. They therefore suggest the slope of the 75th percentile from quantile regression as a correction factor. Newborn Screening assay from Chromsystems was used. 2021
Challenging the status quo: A comparison of ion exchange chromatography with liquid chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry methods for the measurement of amino acids in human plasma The Chromsystems LC-MS/MS assay MassChrom Amino Acid Analysis demonstrated comparable analytical performance and reasonable correlation with ion exchange chromatography (IEC). It also confers practical advantages which cannot be realised by ion exchange chromatography, superior specificity and significantly faster analysis time, suggesting that IEC should no longer be described as the gold standard method for plasma amino acid analysis. 2020
Poster: Newborn Screening for hereditary tyrosinemia type I: succinylacetone isolation without hydrazinesuccinylacetone isolation without hydrazine The novel assay was demonstrated to be accurate
in the detection of newborns with IEM, robust, and above all, without the risk of the exposure to
highly toxic reagents and requirement of additional equipment for toxic fume evacuation.
Short-Term Stability of Amino acids and Acylcarnitines in the Dried Blood Spots Used to Screen Newborns for Metabolic Disorders Low humidity and low temperature conditions are required for transportation and storage of dried blood spots according to that study. MassChrom Amino Acids was used. 2014
Evaluation of a novel, commercially available mass spectrometry kit for newborn screening including succinylacetone without hydrazine Evaluation of the MassChrom Amino Acids and Acylcarnitines assay with SuAC 2012
Poster: NEWBORN SCREENING FOR SUCCINYLACETONE, A PATHOGNOMONIC MARKER FOR TYROSINEMIA TYPE I The objective of this study was to evaluate a validated commercial LC-MS/MS test assaying newborn blood spots for SUAC among other markers for hereditary metabolic disorders. 2011


Please find here publications as guides for reference ranges or therapeutic ranges. They may differ from other published data and are only intended to serve as a rough guide. As data vary depending on patient population and measurement method, please determine ranges for your laboratory. When determining ranges make sure that you comply with local national requirements. 

Title Summary Year
Age-Related Reference Intervals for Blood Amino Acids in Thai Pediatric Population Measured by Liquid Chromatography Tandem Mass Spectrometry Reference intervals of age-specific blood amino acids using LC-MS/MS were established in the Thai pediatric population. They diverge from previous studies, substantiating the recommendation that, for the optimal clinical practice, age-specific reference intervals of amino acids should be designated for the particular population and analysis method. NBS was performed with MassChrom Amino Acids and Acylcarnitines.  2018
Age-Related Reference Intervals for Blood Amino Acids inThai Pediatric Population Measured by LiquidChromatography Tandem Mass Spectrometry MassChrom Amino Acid Test has been used to establish reference intervals of age-specific blood amino acids using LCMS/MS were established in the Tai pediatric population.  2018
Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function The paper discusses values of amino acids such as methionine and their plasma concentration with a patient of adenosine Kinase deficiency.  2011
Age-related Variations in Acylcarnitine and Free Carnitine Concentrations Measured by Tandem Mass Spectrometry Although the risk of underdiagnosis of fatty acid oxidation disorders with the use of newborn values as reference can be considered as small, in some circumstances the use of age-related reference values may have a potential impact on the diagnosis and management of inherited errors of metabolism. 2005
S-adenosylhomocysteine Hydrolase Deficiency in a Human: A Genetic Disorder of Methionine Metabolism The paper discusses biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency. 2004
Blau, N., Duran, M., Blaskovics, M.E., Gibson, K.M. (Eds.). Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases. Springer Verlag (2003).  2003
Significance of L-alloisoleucine in Plasma for Diagnosis of Maple Syrup Urine Disease The present findings indicate that plasma L-alloisoleucine above the cutoff value of 5 micromol/L is the most specific and most sensitive diagnostic marker for all forms of MSUD. 1999
Age-specific distribution of plasma amino acid concentrations in a healthy pediatric population  Variations in amino acid concentrations according to age should be considered by clinical chemists studying amino acids in children. 1997
Shapira E, Blitzer MG, Miller JB, Africk DK (Ed). Diagnostic Tests for Metabolic Disorders. In: Biochemical Genetics – A Laboratory Manual. Pp 94-95. Oxford University Press New York Oxford (1989). Book with reference ranges.  1989