Cribado neonatal de fibrosis quística

Tellería Orriols, J.J.; Alonso Ramos, M.J.; Garrote Adrados, J.A.; Fernández Carvajal, I.; Blanco Quirós, A.

doi:10.1016/S1695-4033(02)77894-6

Información del artículo

Objetivo

Analizar la eficacia del método utilizado para el cribadoneonatal de fibrosis quística en Castilla y León, realizadocon muestras de sangre impregnadas en papel absorbente.

Material y métodos

Se estudiaron 36.086 recién nacidos desde enero de1999 a junio de 2001 mediante cuantificación de tripsinógenoinmunorreactivo (TIR). Cuando los valores fueronsuperiores a 60 ng/ml se buscaron mutaciones en el genCFTR con una cobertura del 87,5% de los alelos mutantesen nuestra población. Se solicitó estudio mediante test delsudor en todos los niños en los que se encontró una mutación.

Resultados

Se detectaron valores de TIR > 60 ng/ml en 285 niños(0,79%), se diagnosticó fibrosis quística en 8/285 (2,8%)y en otros 11/285 (3,9%) se encontró una mutación, contest de sudor negativo, por lo que se consideraron portadoressanos. Hasta la actualidad no se tiene noticia de laaparición de ningún falso negativo.

Conclusiones

El método de cribado en dos fases utilizado cumple loscriterios exigibles con una sensibilidad del 98,5%. El modelogeneral del estudio puede utilizarse en otras comunidades,aunque el rastreo de mutaciones deberá ser optimizadorealizando programas piloto que identifiquen elespectro local de mutaciones de fibrosis quística.

Palabras clave:

CFTR

Cribado neonatal

Fibrosis quística

Mutaciones genéticas

Recién nacido

Tripsinógeno inmunorreactivo

Objective

To analyze the efficiency of the method of neonatalscreening for cystic fibrosis (CF) used in Castille and Leon(Spain), which is carried out with blood from Guthriespots.

Material and methods

A total of 36,086 newborns were studied from January1999 to June 2001. Immunoreactive trypsinogen (IRT) wasquantified in all samples and genetic study covering 87.5%of mutations in the CFTR gene was carried out when IRTlevels were > 60 ng/mL. The sweat test was performed inall children in whom at least one mutation was detected.

Results

IRT values of>60 ng/mL were found in 285 children(0.79%). Of these, eight children (2.8%) were diagnosedwith CF and a further 11 children (3.9%) with a negativesweat test were found to have one mutation and were thusclassified as healthy carriers. To date, no false negativeshave been detected.

Conclusions

The two-stage screening method fulfills the required criteria.Its sensitivity is 98.5% and the basic model can beused in other regions although genetic screening shouldbe optimized by pilot programs to identify the local spectrumof CFTR mutations.

Key words:

CFTR

Neonatal screening

Cystic fibrosis

Genetic mutations

Newborn

Immunoreactive trypsinogen

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Bibliografía

[1.]

T. Casal, M.D. Ramos, J. Gimenez, S. Larriba, V. Nunes, X. Estivill.

High heterogeneity for cystic fibrosis in Spanish families: 75 mutations account for 90% of chromosomes.

Hum Genet, 10 (1997), pp. 365-370

[2.]

E. Coto, C. Bousoño, M.J. Menendez, R. Cue, J.F. Toral, A. Benavides, et al.

Cystic fibrosis in Asturias: An elevated frequency of the delta F508 mutation.

Med Clin, 103 (1994), pp. 681-683

[3.]

J.A. Dodge.

Why screen for cystic fibrosis? A clinicians view.

Acta Paediatr, 32 (1999), pp. 28-32

[4.]

B. Wilcken.

Newborn screening for cystic fibrosis: Its evolution and a review of the current situation.

Screening, 2 (1993), pp. 43-62

[5.]

J.R. Crossley, R.B. Elliot.

Smith PA. Dried blood spot screening for cystic fibrosis in the newborn.

Lancet, 1 (1979), pp. 472-474

Medline

[6.]

J.L. Iovanna, C. Ferec, J. Sarles, J.C. Dagorn.

The pancreatitis-associated protein (PAP). A new candidate for neonatal screening of cystic fibrosis.

C R Acad Sci III, 317 (1994), pp. 561-564

Medline

[7.]

P.M. Farrell, R.A. Aronson, G. Hoffman, R.H. Laessig.

Newborn screening for cystic fibrosis in Wisconsin: First application of population-based molecular genetics testing.

Wis Med J, (1994), pp. 415-421

[8.]

R.G. Gregg, A. Simantel, P.M. Farrell, R. Koscik, M.R. Kosorok, A. Laxova, et al.

Newborn screening for cystic fibrosis in Wisconsin: Comparison of biochemical and molecular methods.

Pediatrics, 99 (1997), pp. 819-824

Medline

[9.]

J. Larsen, S. Campbell, E.B. Faragher, M. Gotz, I. Eichler, S. Waldherr, et al.

Cystic fibrosis screening in neonates–measurement of immunoreactive trypsin and direct genotype analysis for delta F508 mutation.

Eur J Pediatr, 153 (1994), pp. 569-573

Medline

[10.]

E. Dequeker, H. Cuppens, J. Dodge, X. Estivill, M. Goosens, P.F. Pignatti, et al.

Recommendations for quality improvement in genetic testing for cystic fibrosis. European Concerted Action on Cystic Fibrosis.

Eur J Hum Genet, 8 (2000), pp. 2-24

http://dx.doi.org/10.1038/sj.ejhg.5200458 | Medline

[11.]

J.J. Tellerí, M.J. Alonso, C. Calvo, M. Alonso, A. Blanco.

Spectrum of CFTR mutations in the Middle-North of Spain and identification of a novel mutation (1341 G ® A). Mutation in Brief no. 252 Online.

Hum Mutat, 14 (1999), pp. 89

http://dx.doi.org/10.1002/(SICI)1098-1004(1999)14:1<89::AID-HUMU18>3.0.CO;2-5 | Medline

[12.]

P.S. Walch, D.A. Metzger, R. Higuchi.

Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic matherial.

BioTechniques, 10 (1991), pp. 506-513

Medline

[13.]

C. Castellani, M.G. Benetazzo, A. Bonizzato, P.F. Pignatti, G. Mastella.

Cystic fibrosis mutations in heterozygous newborns with hypertrypsinemia and low sweat chloride.

Am J Hum Genet, 64 (1999), pp. 303-304

http://dx.doi.org/10.1086/302212 | Medline

[14.]

Wilson JMG, Jungner G. Principles and practice of screening for disease. Genève: WHO, 1968

[15.]

M. Corey.

Requirements for assesing possible benefits of screening: Fundamental problems of comparing screened and unscreened groups of cystic fibrosis patients.

Proceedings of the International Conference, pp. 289-299

[16.]

J.E. Dankert-Roelse, G.J. Meerman, A. Martijn, L.P. Kate, K. Knol.

Survival and clinical outcome in patients with cystic fibrosis with or without neonatal screening.

J Pediatr, 114 (1989), pp. 362-367

Medline

[17.]

J.E. Dankert-Roelse, G.J. Meerman.

Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre.

Thorax, 50 (1995), pp. 712-718

Medline

[18.]

D.L. Waters, B. Wilcken, L. Irwing, P. Van Asperen, C. Mellis, J.M. Simpson, et al.

Clinical outcomes of newborn screening for cystic fibrosis.

Arch Dis Child Fetal Neonatal, 80 (1999), pp. 1-7

[19.]

P.M. Farrell, M.R. Kosorok, A. Laxova, G. Shen, R.E. Koscik, W.T. Bruns, et al.

Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

N Engl J Med, 337 (1997), pp. 963-969

http://dx.doi.org/10.1056/NEJM199710023371403 | Medline

[20.]

S. Chatfield, G. Owen, H.C. Ryley, J. Williams, M. Alfaham, M.C. Goodchild, et al.

Neonatal screening for cystic fibrosis in Wales and the West Midlands: Clinical assessment after five years of screening.

Arch Dis Child, 66 (1991), pp. 29-33

Medline

[21.]

J. Feingold, M. Guilloud-Bataille, D. De Crozes.

Neonatal screening for cystic fibrosis in France: Possible reduced morbidity in detected patients.

Neonatal screening for cystic fibrosis. Proceedings of the International Conference Caen, pp. 275

[22.]

T. Dudding, B. Wilcken, B. Burgess, G. Turner.

Neonatal screening for cystic fibrosis.

Lancet, (2000), pp. 356-1930

http://dx.doi.org/10.1016/S0140-6736(06)68074-4 | Medline

[23.]

T. Dudding, B. Wilcken, B. Burgess, J. Hambly, G. Turner.

Reproductive decissions after neonatal screening identifies cystic fibrosis.

Arch Dis Child Fetal Neonatal, 82 (2000), pp. 124-127

[24.]

C. Vázquez.

Diagnóstico de la fibrosis quística.

An Esp Pediatr, 50 (1999), pp. 431-438

Medline

[25.]

T. Dudding, B. Wilcken, B. Burgess, G. Turner.

Neonatal screening for cystic fibrosis.

Lancet, (2000), pp. 356-1930

http://dx.doi.org/10.1016/S0140-6736(06)68074-4 | Medline

[26.]

X. Estivill, C. Bancells, C. Ramos.

and the Biomed CF Mutation Analysis Consortium. Geografic distribution and regional origin of 272 cystic fibrosis mutations in european populations.

Hum Mutat, 10 (1997), pp. 135-154

http://dx.doi.org/10.1002/(SICI)1098-1004(1997)10:2<135::AID-HUMU6>3.0.CO;2-J | Medline

El programa de cribado neonatal de fibrosis quística está financiado por la Consejería de Sanidady Bienestar Social de la Junta de Castilla y León.

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