Defectos del tubo neural y ácido fólico: patogenia, metabolismo y desarrollo embriológico. Revisión de la literatura

Autores/as

  • Fernando Suárez-Obando
  • Adriana Ordóñez-Vásquez
  • Ignacio Zarante

DOI:

https://doi.org/10.18597/rcog.307

Palabras clave:

defectos del tubo neural, ácido fólico, regulación del desarrollo de la expresión génica, malformaciones del sistema nervioso

Resumen

Introducción: el uso del ácido fólico preconcepcional para la prevención de los defectos del tubo neural (DTN), es una medida de gran impacto en la salud pública. El objetivo de esta revisión es describir el modelo de desarrollo embriológico de los DTN y los mecanismos por los cuales el ácido fólico disminuye su prevalencia.

Metodología: se realizó una búsqueda de la literatura en las bases de datos MEDLINE/PubMed, OVID, LILACS y SciELO de las cuales se seleccionaron los artículos que permitieran reconstruir la fisiopatología de la enfermedad, incluyendo la embriología y la presentación clínica y destacando el papel del ácido fólico en la proliferación celular y en el proceso de neurulación.

Resultados: se presenta la fisiopatología de los DTN y se describe la relación entre la disminución de la concentración de acido fólico y la neurulación fallida.

Conclusiones: el modelo propuesto es útil para entender el desarrollo de los DTN y se resalta el efecto del consumo de ácido fólico sobre la salud materno-fetal.

Biografía del autor/a

Fernando Suárez-Obando

Grupo Ácido Fólico (GAF), Instituto de Genética Humana, Pontificia Universidad Javeriana. Carrera 7ª N° 40-62, edificio 32. Bogotá (Colombia).

Adriana Ordóñez-Vásquez

Grupo Ácido Fólico (GAF), Instituto de Genética Humana, Pontificia Universidad Javeriana. Carrera 7ª N° 40-62, edificio 32. Bogotá (Colombia).

Ignacio Zarante

Grupo Ácido Fólico (GAF), Instituto de Genética Humana, Pontificia Universidad Javeriana. Carrera 7ª N° 40-62, edificio 32. Bogotá (Colombia).

Referencias bibliográficas

Copp AJ, Greene ND. Genetics and development of neural tube defects. J Pathol 2010;220:217-30.

Hibbard ED, Smithells RW. Folic acid metabolism and human embryopathy. Lancet 1965;1:254.

Smithells RW, Sheppard S, Schorah CJ, Seller MJ, Nevin NC, Harris R, et al. Apparent prevention of neural tube defects by periconceptional vitamin supplementation. Arch Dis Child 1981;56:911-8.

Wilson RD, Johnson JA, Wyatt P, Allen V, Gagnon A, Langlois S, et al. Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and The Motherrisk Program. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 2007;29:1003-26.

Ordóñez A, Suárez F. Exploración sobre los conocimientos del ácido fólico y sus beneficios en la salud reproductiva en una población universitaria colombiana. Rev Colomb Obstet Ginecol 2006;57:271-8.

Bryce J, Coitinho D, Darnton-Hill I, Pelletier D, Pinstrup-Andersen P. Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: effective action at national level. Lancet 2008;371:510-26.

Parra BE, Manjarrés LM, Gómez AL, Alzate DM, Jaramillo MC. Assessment of nutritional education and iron supplement impact on prevention of pregnancy anemia. Biomedica 2005;25:211-9.

Botto LD, Moore CA, Khoury MJ, Erickson JD.Neural tube defects. N Engl J Med 1999;341:1509-19.

Kramer MS. The epidemiology of adverse pregnancy outcomes: an overview. J Nutr 2003;133:1592S-1596S.

Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, et al. National Birth Defects Prevention Network. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol 2008;82:527-32.

Shurtleff DB. Epidemiology of neural tube defects and folic acid. Cerebrospinal Fluid Res 2004;1:5.

Morris JK, Wald NJ. Quantifying the decline in the birth prevalence of neural tube defects in England and Wales. J Med Screen 1999;6:182-5.

Calvo E, Biglieri A. Impact of folic acid fortification on women nutritional status and on the prevalence of neural tube defects. Arch Argent Pediatr 2008;106:492-8.

Nazer HJ, Cifuentes OL, Aguila RA, Juárez ME, Cid MP, Godoy ML, et al. Effects of folic acid fortification in the rates of malformations at birth in Chile. Rev Med Chil 2007;135:198-204.

Castilla EE, Orioli IM, López-Camelo JS, Dutra Mda G, Nazer-Herrera J. Latin American Collaborative Study of Congenital Malformations (ECLAMC). Preliminary data on changes in neural tube defect prevalence rates after folic acid fortification in South America. Am J Med Genet A 2003;123A:123-8.

World Health Organization. World Atlas of Birth Defects. Geneva, Switzerland; 2003.

Fernández N, Zarante I. Prevalencia y escala pronóstico para malformaciones congénitas en Colombia: La responsabilidad de pediatras y neonatólogos. Registro de 54.397 nacimientos. UCIN 2007;7:28-32.

República de Colombia. Decreto Número 1944 de 1996.

Williams LJ, Rasmussen SA, Flores A, Kirby RS, Edmonds LD. Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995-2002. Pediatrics 2005;116:580-6.

Shin M, Besser LM, Correa A. Prevalence of spina bifida among children and adolescents in metropolitan Atlanta. Birth Defects Res A Clin Mol Teratol 2008;82:748-54.

Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999;341:1485-90.

Beaudin AE, Stover PJ. Insights into metabolic mechanisms underlying folate-responsive neural tube defects: a minireview. Birth Defects Res A Clin Mol Teratol 2009;85:274-84.

Greene ND, Copp AJ. Development of the vertebrate central nervous system: formation of the neural tube. Prenat Diagn 2009;29:303-11.

Saitsu H, Yamada S, Uwabe C, Ishibashi M, Shiota K. Development of the posterior neural tube in human embryos. Anat Embryol (Berl) 2004;209:107-17.

Kibar Z, Capra V, Gros P. Toward understanding the genetic basis of neural tube defects. Clin Genet 2007;71:295-310.

Ybot-González P, Savery D, Gerrelli D, Signore M, Mitchell CE, Faux CH, et al. Convergent extension, planar-cell-polarity signaling and initiation of mouse neural tube closure. Development 2007;134:789-99.

Ybot-González P, Gaston-Massuet C, Girdler G, Klingensmith J, Arkell R, Greene ND, et al. Neural plate morphogenesis during mouse neurulation is regulated by antagonism of BMP signalling. Development 2007;134:3203-11.

Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2008;2:1-13.

Monteiro R, van Dinther M, Bakkers J, Wilkinson R, Patient R, ten Dijke P, et al. Two novel type II receptors mediate BMP signaling and are required to establish left-right asymmetry in zebrafish. Dev Biol 2008;315:55-71.

Olsen SK, Garbi M. Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs". J Biol Chem 2003;278:34226-36.

Doudney K, Stanier P. Epithelial cell polarity genes are required for neural tube closure. Am J Med Genet C Semin Med Genet 2005;135C:42-7.

Copp AJ. Neurulation in the cranial region-normal and abnormal. Anat 2005; 207:623-35.

Iang XB, Iseki S, Maxson RE, Sucov HM, Morriss-Kay GM. Tissue origins and interactions in the mammalian skull vault. Dev Biol 2002;241:106-16.

Melnick M, Myrianthopoulos NC. Studies in neural tube defects II. Pathologic findings in a prospectively collected series of anencephalics. Am J Med Genet 1987;26:797-810.

Aleksic S, Budzilovich G, Greco MA, Feigin I, Epstein F, Pearson J. Iniencephaly: a neuropathologic study. Clin Neuropathol 1983;2:55-61.

Hoving EW, Vermeij-Keers C. Frontoethmoidal encephaloceles: a study of their pathogenesis. Pediatr Neurosurg 1997;27:246-56.

Greene ND, Copp AJ. Development of the vertebrate central nervous system: formation of the neural tube. Prenat Diagn 2009;29:303-11.

Dias MS. Normal and abnormal development of the spine. Neurosurg Clin N Am 2007;18:415-29.

Warkany J, O'Toole BA. Experimental spina bifida and associated malformations. Childs Brain 1981;8:18-30.

Ybot-González P, Cogram P, Gerrelli D, Copp AJ. Sonic hedgehog and the molecular regulation of mouse neural tube closure. Development 2002;129:2507-17.

Stottmann RW, Berrong M, Matta K, Choi M, Klingensmith J. The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol 2006;295:647-63.

Deak KL, Siegel DG, George TM, Gregory S, Ashley-Koch A, Speer MC. NTD Collaborative Group. Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects. Birth Defects Res A Clin Mol Teratol 2008;82:662-9.

Zlotogora J. Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am J Med Genet 1997;68:472-5.

Oyen N, Boyd HA, Poulsen G, Wohlfahrt J, Melbye M. Familial recurrence of midline birth defects: a nationwide danish cohort study. Am J Epidemiol 2009;170:46-52.

Kondo A, Kamihira O, Ozawa H. Neural tube defects: prevalence, etiology and prevention. Int J Urol 2009;16:49-57.

Larmarcovai G, Bonassi S, Botta A, Baan RA, Orsière T. Genetic polymorphisms and micronucleus formation: a review of the literature. Mutat Res 2008;58:215-33.

Thomas P, Fenech M. Methylenetetrahydrofolate reductase, common polymorphisms, and relation to disease. Vitam Horm 2008;79:375-92.

Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001;409:928-33.

DeVos L, Chanson A, Liu Z, Ciappio ED, Parnell LD, Mason JB, et al. Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations. Am J Clin Nutr 2008;88:1149-58.

Christensen B, Arbour L, Tran P, Leclerc D, Sabbaghian N, Platt R, et al. Genetic polymorphisms in Methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet 1999;84:151-7.

van der Put NM, Steegers-Theunissen RP, Frosst P, et al. Mutated Methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995;346:1070-1.

Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000;151:862-77.

International clearinghouse for birth defects monitoring systems. Annual report 2001 with data for 1999. Roma: International Centre for Birth Defects; 2001.

Wilcken B, Bamforth F, Li Z, et al. Geographic and ethnic variation of the 677C T allele of 5,10 Methylenetetrahydrofolate reductase (MTHFR): Findings from over 7,000 newborns from 16 areas world wide. J Med Genet 2003;40:619-25.

VollsetSE,BottoL.NeuralTubeDefects.Othercongenital malformations and single nucleotide polymorphisms in the 5,10 Methylenetetrahydrofolate reductase (MTHFR) gene: A Meta-Analysis En: Rozen Ueland PM, Rozen R, eds. MTHFR Polymorphisms and Disease. Georgetown. Landes Boscience 2005. p. 125-43.

Christensen B, Arbour L, Tran P, Leclerc D, Sabbaghian N, Platt R, et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet 1999;84:151-7.

Barbosa PR, Stabler SP, Machado AL, Braga RC, Hirata RD, Hirata MH, et al. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr 2008;62:1010-21.

Gos M Jr, Szpecht-Potocka A. Genetic basis of neural tube defects II. Genes correlated with folate and methionine metabolism. J Appl Genet 2002;43:511-24.

Newton R, Loughna SC, Stanier PM. Jensson O, Moore GE. X-linked spina bifida: a linkage analysis. (Series) Miami Short Reports. Advances in Gene Technology: The Molecular Biology of Human Genetic Disease. New York: IRL Press 1; 1991. p. 33.

Rothenberg SP, da Costa MP, Sequeira JM, Cracco J, Roberts JL, Weedon J, et al. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 2004;350:134-42.

Chen Z, Karaplis AC, Ackerman SL. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 2001;10:433-43.

Fujinaga M, Baden JM. Methionine prevents nitrous oxide-induced teratogenicity in rat embryos grown in culture. Anesthesiology 1994;81:184-9.

Gu L, Wu J, Qiu L, Jennings CD, Li GM. Involvement of DNA mismatch repair in folate deficiency induced apoptosis small star, filled. J Nutr Biochem 2002;13:355-63.

Wen S, Lu W, Zhu H, Yang W, Shaw GM, Lammer EJ, et al. Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida. Am J Med Genet A 2009;149A:155-60.

Ifergan I, Assaraf YG. Molecular mechanisms of adaptation to folate deficiency. Vitam Horm 2008;79:99-143.

Patterson D, Graham C, Cherian C, Matherly LH. A humanized mouse model for the reduced folate carrier. Mol Genet Metab 2008;93:95-103.

Cómo citar

1.
Suárez-Obando F, Ordóñez-Vásquez A, Zarante I. Defectos del tubo neural y ácido fólico: patogenia, metabolismo y desarrollo embriológico. Revisión de la literatura. Rev. colomb. obstet. ginecol. [Internet]. 30 de marzo de 2010 [citado 28 de marzo de 2024];61(1):49-60. Disponible en: https://revista.fecolsog.org/index.php/rcog/article/view/307

Descargas

Los datos de descargas todavía no están disponibles.

Descargas

Publicado

2010-03-30

Número

Sección

Artículo de Revisión
QR Code

Métricas

Estadísticas de artículo
Vistas de resúmenes
Vistas de PDF
Descargas de PDF
Vistas de HTML
Otras vistas