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 Quibdó cities is described.
Results: fifty seven analytes that allow the diagnosis of 50 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 2-18 days of age were included, 523 from Cali and 368 from Quibdó; 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.
Authors
Downloads
Keywords
- Neonatal Screenings
- inborn errors
- amino acids
- acylcarnitines
- Succinylacetone
- Mass Spectrometry
- Tandem
References
Hernández DC. Tamizaje neonatal por espectrometría de masas en tándem: actualización. Rev Panam Salud Publica. 2010; 27(4): 309-17.
van Karnebeek CD, Stockler-Ipsiroglu S. Early identification of treatable inborn errors of metabolism in children with intellectual disability: The Treatable Intellectual Disability Endeavor protocol in British Columbia. Paediatr Child Health. 2014; 19(9): 469-71.
Cifuentes Y, Bermúdez M, Arteaga C. Neonathal encefhalopathy something more that perinatal asphysia. Rev Fac Med Univ Nacional Colomb. 2007; 55(2): 126-34.
Chace DH, Kalas TA, Naylor EW. Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem. 2003; 49(11): 1797-817
Therrell BL, Padilla CD, Loeber JG, Kneisser I, Saadallah A, Borrajo GJ, et al. Current status of newborn screening worldwide: 2015. Seminars Perinatol. 2015; 39(3): 171-87.
Millington DS, Roe CR, Maltby DA. Application of high resolution fast atom bombardment and constant B/E ratio linked scanning to the identification and analysis of acylcarnitines in metabolic disease. Biomed Mass Spectrom. 1984; 11(5): 236-41.
Millington DS, Norwood DL, Kodo N, Roe CR, Inouet F. Application of fast atom bombardment with tandem mass spectrometry and liquid chromatography/mass spectrometry to the analysis of acylcarnitines in human urine, blood, and tissue. Analyt Biochem. 1989; 180(2): 331-9.
Chace DH, Sherwin JE, Hillman SL, Lorey F, Cunningham GC. Use of phenylalanine-to-tyrosine ratio determined by tandem mass spectrometry to improve newborn screening for phenylketonuria of early discharge specimens collected in the first 24 hours. Clin Chem. 1998; 44(12): 2405-9.
Jensen UG, Brandt NJ, Christensen E, Skovby F, Nørgaard-Pedersen B, Simonsen H. Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study. Clin Chem. 2001; 47(8): 1364-72.
Chace DH, Lim T, Hansen CR, De Jesus VR, Hannon WH. Improved MS/MS analysis of succinylacetone extracted from dried blood spots when combined with amino acids and acylcarnitine butyl esters. Clin Chim Acta.2009; 407(1-2): 6-9.
Dhillon KS, Bhandal AS, Aznar CP, Lorey FW, Neogi P. Improved tandem mass spectrometry (MS/MS) derivatized method for the detection of tyrosinemia type I, amino acids and acylcarnitine disorders using a single extraction process. Clin Chim Acta. 2011; 412(11): 873-9.
Raghuveer TS, Garg U, Graf WD. Inborn errors of metabolism in infancy and early childhood: an update. Am Fam Physician. 2006; 73(11): 1981-90.
Applegarth DA, Toone JR. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000; 105(1): e10-e.
Schulze A, Lindner M, Kohlmüller D, Olgemöller K, Mayatepek E, Hoffmann GF. Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics. 2003; 111(6): 1399-406.
Couce ML, Castiñeiras DE, Bóveda MD, Baña A, Cocho JA, Iglesias AJ, et al. Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme. Mol Genet Metab. 2011; 104(4): 470-5.
Torres-Sepúlveda MdR, Martínez-de Villarreal LE, Esmer C, González-Alanís R, Ruiz-Herrera C, Sánchez-Peña A, et al. Tamiz metabólico neonatal por espectrometría de masas en tándem: dos años de experiencia en Nuevo León, México. Sal Públ Méx. 2008; 50(3): 200-6.
Borrajo GJC. Newborn screening in Latin America at the beginning of the 21st century. J Inherit Metab Dis. 2007; 30(4): 466-81.
De Céspedes C, Saborío M, Trejos R, Casco T. Prevención de retardo mental y otras discapacidades por tamizaje neonatal masivo en Costa Rica. Costa Rica: Asociación Costarricense para el Tamizaje y la Prevención de Discapacidades en el Niño (ASTA). 2003.
Rosselli D, Rueda JD, Ruiz-Patiño A. Análisis de costos de la tamización neonatal universal mediante espectrometría de masas en tándem para errores innatos del metabolismo en Colombia. Pediatría. 2014; 47(03): 68-73.
CLSI. Blood Collection on Filter Paper for Newborn Screening Programs; Approved Standard - Sixth Edition. CLSI document NBS01-A6. Wayne, PA: The Clinical and Laboratory Standards Institute 2013.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM). Guidance for Industry: Bioanalytical Method Validation. Available from: https://www.fda.gov/downloads/Drugs/Guidance/ucm070107.pdf. 2001.
Berry SA, Jurek AM, Anderson C, Bentler K. The inborn errors of metabolism information system: a project of the Region 4 Genetics Collaborative Priority 2 Workgroup. Genetics Med. 2010;1 2: S215-S9.
DANE. Rendición de cuentas 2014-2015. Estadísticas vitales. 2015. Available from: https://www.dane.gov.co/files/rendicion_cuentas
/Informe%20Rendicion%20de%20cuentas%202015.pdf.
CLSI. How to Define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline. Second Edition. NCCLS document C28-A2 Wayne, PA: The Clinical and Laboratory Standards Institute; 2000.
Chace DH, Hillman SL, Van Hove JL, Naylor EW. Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin Chem. 1997; 43(11): 2106-13.
Chace DH, DiPerna JC, Mitchell BL, Sgroi B, Hofman LF, Naylor EW. Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem. 2001; 47(7): 1166-82.
Cavedon CT, Bourdoux P, Mertens K, Van Thi HV, Herremans N, de Laet C, et al. Age-related variations in acylcarnitine and free carnitine concentrations measured by tandem mass spectrometry. Clin Chem. 2005; 51(4): 745-52.
Gong ZH, Tian GL, Wang YM. Blood spot carnitine and acylcarnitine in newborn to adolescence: measured by tandem mass spectrometry. Zhonghua Er Ke Za Zhi. 2010; 48(12): 922-7.
CLSI. Newborn Screening by Tandem Mass Spectrometry; Approved Guideline. CLSI document NBS04. Wayne, PA.: The Clinical and Laboratory Standards Institute; 2010.
Wagner M, Tonoli D, Varesio E, Hopfgartner G. The use of mass spectrometry to analyze dried blood spots. Mass Spectrom Rev. 2016; 35(3): 361-438.
Golbahar J, Altayab DD, Carreon E. Short-term stability of amino acids and acylcarnitines in the dried blood spots used to screen newborns for metabolic disorders. J Med Screen. 2014; 21(1): 5-9.
Lawson AJ, Bernstone L, Hall SK. Newborn screening blood spot analysis in the UK: influence of spot size, punch location and haematocrit. J Med Screen. 2016; 23(1): 7-16.
Holub M, Tuschl K, Ratschmann R, Strnadova KA, Muhl A, Heinze G, et al. Influence of hematocrit and localisation of punch in dried blood spots on levels of amino acids and acylcarnitines measured by tandem mass spectrometry. Clin Chim Acta. 2006; 373(1-2): 27-31..
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use
