Analysis of serum amino acid profile in Cuban patients with clinical manifestations of aminoacidopathies
DOI:
https://doi.org/10.56294/piii2025372Keywords:
Aminoacidopathies, Amino Acid Profiles, HPLC-RP, Clinical Manifestations, Biochemical DiagnosisAbstract
Introduction: aminoacidopathies are a group of inborn errors of metabolism caused by defects in metabolic pathways involving amino acids. Quantification of serum amino acids is necessary for the diagnosis of these defects.
Objective: to analized the serum amino acid profile in patients with clinical manifestations of aminoacidopathies.
Methods: an observational, descriptive, prospective case series study was carried out. 32 pediatric patients of both sexes with clinical manifestation of aminoacidopathies from 9 provinces of the country treated in specialized Clinical Genetics clinics were included. The samples were sent to the Biochemical Genetics Laboratory of the National Center for Medical Genetics in the period between January 2023 and June 2024. Ten serum amino acids were quantified by a High-Performance Reverse-Phase Liquid Chromatography method and pre-column derivatization with o-phthaldehyde implemented in the Laboratory.
Results: in the sample studied, the male sex predominated and the largest number of cases was contributed by the province of Havana. 53 % of the patients corresponded to the age group of 1 to 6 years. Neurological alterations and metabolic acidosis were the mains reasons for requesting a serum aminogram. In 59 % of the cases (19/32), significant alterations in the amino acid profile were identified, which allowed the identification of several types of aminoacidopathies as a possible diagnosis of the cases studied.
Conclusions: the analysis of the serum amino acid profile is essential for the diagnosis of aminoacidopathies in patients with clinical alterations suggestive of these entities
References
1. Piombarolo A, Ialongo C, Bizzarri M, Angeloni A. Systems Biology and Inborn Error of Metabolism: Analytical Strategy in Investigating Different Biochemical/Genetic Parameters. En: Bizzarri M, editor. Systems Biology, vol. 2745, New York, NY: Springer US; 2024, p. 191-210. https://doi.org/10.1007/978-1-0716-3577-3_12.
2. Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M, Ayesha H. Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options. Biochem Genet 2018;56:7-21. https://doi.org/10.1007/s10528-017-9825-6.
3. Dalili S, Talea A, Aghajany-Nasab M, Alirezapour Asl Miandoab N, Koohmanaee S, Hakemzadeh ST, et al. Clinical Features and Laboratory Diagnosis of Aminoacidopathies: A Narrative Review. Arch Neurosci 2023;10. https://doi.org/10.5812/ans-136721.
4. Cunningham G, Zhou Y, Summar M. Development of a robust 30-minute reverse-phase high pressure liquid chromatography method to measure amino acids using widely available equipment and its comparison to current clinical ion-exchange chromatography measurement. Molecular Genetics and Metabolism Reports 2022;31:100868. https://doi.org/10.1016/j.ymgmr.2022.100868.
5. Ding S, Han L. Newborn screening for genetic disorders: Current status and prospects for the future. Pediatric Investigation 2022;6:291-8. https://doi.org/10.1002/ped4.12343.
6. Liu H. Measurement of Blood Plasma Amino Acids in Ultrafiltrates by High-Performance Liquid Chromatography with Automatic Precolumn O-Phthaldialdehyde Derivatization. Amino Acid Analysis Protocols, vol. 159, New Jersey: Humana Press; 2000, p. 123-40. https://doi.org/10.1385/1-59259-047-0:123.
7. Babu SVS, Shareef MM, Shetty APK, Shetty KT. HPLC method for amino acids profile in biological fluids and inborn metabolic disorders of aminoacidopathies. Indian J Clin Biochem 2002;17:7-26. https://doi.org/10.1007/BF02867967.
8. Imanzadeh F, Emadi B, Rohani P, Hosseini A, Khatami K, Dara N, et al. Assessment of Serum Amino Acid Chromatography in Children with Inflammatory Bowel Diseases. Ijp ; Int J Pediatr 2018. https://doi.org/10.22038/ijp.2018.33721.2981.
9. WMA - The World Medical Association-WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Participants s. f. https://www.wma.net/policies-post/wma-declaration-of-helsinki/ (accedido 26 de noviembre de 2024).
10. Merinero B, Pérez‐Cerdá C, Ruiz Sala P, Ferrer I, García MJ, Martínez Pardo M, et al. Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy. J of Inher Metab Disea 2006;29:685-685. https://doi.org/10.1007/s10545-006-0342-8.
11. Belmont-Martínez L, Ibarra-González I, Vela-Amieva M, Guillén-López S, López-Mejía L, Castillo-Razo IR, et al. Causas de hospitalización de pacientes con errores innatos del metabolismo intermediario: análisis de una serie de casos de un hospital de tercer nivel de atención. APM 2020;41. https://doi.org/10.18233/APM41No3pp105-1142065.
12. Tamayo Chang VJ, Morales Peralta E, Santana Hernández EE, Lantigua Cruz PA, Collazo Mesa T, Lardoeyt Ferrer R. Epidemiological and population genetic characterization of fucosidosis in Holguin province, Cuba. Salud, Ciencia y Tecnología - Serie de Conferencias 2024;3:978. https://doi.org/10.56294/sctconf2024978.
13. Osorio JH, Loango Chamorro N, Landázuri P. El tamizaje metabólico en el diagnóstico de los errores innatos del metabolismo. biosalud 2008;7:131-40.
14. Janečková H, Hron K, Wojtowicz P, Hlídková E, Barešová A, Friedecký D, et al. Targeted metabolomic analysis of plasma samples for the diagnosis of inherited metabolic disorders. Journal of Chromatography A 2012;1226:11-7. https://doi.org/10.1016/j.chroma.2011.09.074.
15. Amaral AU, Wajner M. Pathophysiology of maple syrup urine disease: Focus on the neurotoxic role of the accumulated branched-chain amino acids and branched-chain α-keto acids. Neurochemistry International 2022;157:105360. https://doi.org/10.1016/j.neuint.2022.105360.
16. Wongkittichote P, Edmondson A, Hong X. Thymine Hyperexcretion in a Patient with Abnormal Newborn Screen for Glutaric Aciduria Type I. Clinical Chemistry 2023;69:431-2. https://doi.org/10.1093/clinchem/hvac212.
17. Buerger C, Garbade SF, Dietrich Alber F, Waisbren SE, McCarter R, Kölker S, et al. Impairment of cognitive function in ornithine transcarbamylase deficiency is global rather than domain‐specific and is associated with disease onset, sex, maximum ammonium, and number of hyperammonemic events. J of Inher Metab Disea 2019;42:243-53. https://doi.org/10.1002/jimd.12013.
18. Rhim HC, Kim SJ, Park J, Jang K-M. Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis. Journal of Sport and Health Science 2020;9:553-61. https://doi.org/10.1016/j.jshs.2020.02.003.
19. Wajner M, Vargas CR, Amaral AU. Disruption of mitochondrial functions and oxidative stress contribute to neurologic dysfunction in organic acidurias. Archives of Biochemistry and Biophysics 2020;696:108646. https://doi.org/10.1016/j.abb.2020.108646.
20. Tangeraas T, Constante JR, Backe PH, Oyarzábal A, Neugebauer J, Weinhold N, et al. BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening. Brain 2023;146:3003-13. https://doi.org/10.1093/brain/awad010.
21. Kanavin OJ, Woldseth B, Jellum E, Tvedt B, Andresen BS, Stromme P. 2-methylbutyryl-CoA dehydrogenase deficiency associated with autism and mental retardation: a case report. J Med Case Reports 2007;1:98. https://doi.org/10.1186/1752-1947-1-98.
22. Sjarif DR, Ploos Van Amstel JK, Duran M, Beemer FA, Poll‐The BT. Isolated and contiguous glycerol kinase gene disorders: A review. J of Inher Metab Disea 2000;23:529-47. https://doi.org/10.1023/A:1005660826652.
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Copyright (c) 2025 Jessica Laura Páez Campos, Gretel Riverón Forment, Tatiana Acosta Sánchez, Laritza Martínez Rey, Lilia C. Marín Padrón , Ivette Camayd Viera, Iovana Fuentes Cortes, Grettel Huertas Pérez (Author)
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