CYSTIC FIBROSIS: THE HIGHEST PRESENCE OF ATYPICAL FORMS

Ana Estefanía FERNÁNDEZ-LORENZO, Ana MORENO-ÁLVAREZ, Alfonso SOLAR-BOGA, Cristóbal COLÓN-MEJERAS, Francisco BARROS-ANGUEIRA, Josep SIRVENT-GÓMEZ, María Lourdes COUCE, Rosaura LEIS

Abstract


CF (Cystic Fibrosis) is the most common autosomal recessive disease in caucasian population. Inadequate ion transport causes dehydration and the production of thick secretions in organs (most affected: pancreas and lungs). We compare patients between 0-18 years depending on the diagnostic method: neonatal screening (current) versus conventional symptom-oriented diagnosis (prior to 2003). A total of 39 patients (21 boys and 18 girls, median age 8.55 years) were included. 53.8% of the patients were diagnosed by neonatal screening. In the screening group we found greater genetic variability, lower sweat chloride levels, higher vitamin D levels and better nutritional status at time of diagnosis. In their evolution, a better lung function was seen in the screening group. 20.5% of patients present atypical forms of the disease. This group presents milder symptomatology, all of them being sufficient pancreatic at the time of diagnosis. Conclusion: Patients with CF diagnosed through neonatal screening have a better analytical, nutritional and pulmonary status at the onset of the disease and in its evolution. Detection of atypical forms, in a percentage not described before, may explain part of the results found in our study although the benefit of early diagnosis is also seen in the classic forms.


Keywords


BMI: Body Mass Index; CF: Cystic Fibrosis; CFTR: Cystic Fibrosis Transmembrane Conductance Regulator gene

References


Abman SH, Ogle J, Horbeck R, Butler-Simon N, Hammond K, Accurso F (1991). Early bacteriological, immunologic and clinical courses of young infants with cystic fibrosis identified by neonatal screening. J Pediatr 119:211-7.

Alonso M, Heine Suner D, Calvo M, Rosell J, Gimenez J, Ramos M, et al. (2006). Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry. Ann Hum Genet 71(2):194-201.

Borrego S, Casals T, Dapena J, Fernandez E, Gimenez J, Cabeza JC, Sanchez J, Antiñolo G. (1994). Molecular and clinical analyses of cystic fibrosis in the south of Spain. Clin Genet 46: 287-290

Boyle MP (2003). Non classic cystic fibrosis and CFTR-related diseases. Curr Opin Pulm Med 9:498.

Campbell III PW, White TB (2005). Newborn screening for cystic fibrosis: an opportunity to improve care and outcomes. J Pediatr 147(3 Suppl.):S2–5.

Casals T, Ramos MD, Gimenez J, Larriba S, Nunes V, Estivill X (1997). High heterogeneity for cystic fibrosis in Spanish families: 75 mutation account for 90% of chromosomes. Hum Genet 101(3):365-70.

Castellani C, Cuppens H, Macek Jr M, Cassiman J, E. Kerem, P. Durie, et al. (2008) Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros 7:179-96.

CFGAC (1994): The Cystic Fibrosis Genetic Analysis Consortium. Population variation of common cystic fibrosis mutations. Hum Mutat 4:167-77.

Comeau MA, Accurso FJ, White TB, Campbell PW, Hoffman G, Parad RB et al. (2007). Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation Workshop Report. Pediatrics 119: e495- e518.

Conneally PM, Merritt AD, Yu PL (1973). Cystic fibrosis: population genetics. Tex Rep Biol Med 31:639-50.

Consejo Asesor de Cribado Neonatal de Enfermedades Congénitas de la CAPV. Protocolo de cribado neonatal de la fibrosis quística y descripción del programa actual de cribado neonatal de la CAPV. Vitoria-Gasteiz: Osakidetza, Departamento de Sanidad y Consumo del Gobierno Vasco; 2009.

Crossley JR, Smith PA, Edgar BW, Gluckman PK, Elliott RB (1981). Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots. Clin Chim Acta 113:111-21.

Cystic Fibrosis Mutation Database: http://www.genet.sickkids.on.ca/cftr. Last access date: 30/12/2018.

Cystic Fibrosis Foundation Patient Registry. 2016 Annual Data Report. Bethesda, Maryland.

De Marco ML, Dietzen DJ, Brown SM (2015). Sweating the small stuff: adequacy and accuracy in sweat chloride determination. Clin Biochem 46 (6):443-7.

Farrell PM, Lai HJ, Li Z, Kosorok MR, Laxova A, Green CG, et al (2005). Evidence on improved outcomes with early diagnosis of cystic fibrosis through neonatal screening: enough is enough! J Pediatr 147:30–6 [S].

Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, et al. (2004) CDC newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 53(RR-13):1–36.

Grosse SD, Boyle CA, Cordero JF (2005). Newborn screening for cystic fibrosis: recommendations from the Centers for Disease Control and Prevention. Am Fam Physician 71(8):1482–7.

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al. (2005). Standardisation of spirometry. Eur Respir J. 26:319-338.

Ooi CY, Dupuis A, Ellis L, et al (2012). Comparing the American and European diagnostic guidelines for cystic fibrosis: same disease, different language? Thorax 67:618.

Paz Valiñas L. Cribado neonatal de la fibrosis quística. Eficacia/efectividad y protocolos de implementación. Red Española de Agencias de Evaluación de Tecnologías y Prestaciones del SNS. Santiago de Compostela: Axencia de Avaliación de Tecnoloxías Sanitarias de Galicia, Avalia-t. Consellería de Sanidade; 2013.

Pourfarzam M, Zadhoush F (2013). Newborn Screening for inherited metabolic disorders; news and views. J Res Med Sci 18(9): 801–808.

Rueegg CS, Kuehni CE, Gallati S, Baumgartner M, Torresani T, Barben J (2013). One- year evaluation of a neonatal screening program for cystic fibrosis in Switzerland. Dtsch Arztebl Int 110(20):356-63

Salcedo A, Gartner S, Girón RM, García MD. 2012. Tratado de Fibrosis Quística, Editorial Justim SL, Barcelona.

Sheppard DN, Rich DP, Ostedgaard LS, Gregory RJ, Smith AE, Welsh MJ (1993). Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties. Nature 362:160-4.

Siret D, Bretaudeau G, Branger B, et al. (2003). Comparing the clinical evolution of cystic fibrosis screened neonatally to that of cystic fibrosis diagnosed from clinical symptoms: a 10-year retrospective study in a French region Brittany. Pediatr Pulmonol 35: 342–49.

Telleria JJ, Alonso MJ, y Blanco A (2005). Cribado neonatal de la fibrosis quística. An Pediatr Contin 3:168-72)

Van den Akker ME, Dankert HM, Verkerk PH and Dankert JE (2006). Cost- effectiveness of 4 neonatal screening strategies for Cystic Fibrosis. Pediatrics.118: 896-905

Wagener JS, Zemanick ET, Sontag MK (2012). Newborn screening for cystic fibrosis. Curr Opin Pediatr 24(3):329-35.

Wilcken B (2012). Screening for disease in the newborn: the evidence base for blood-spot screening. Pathology 44:73–9.

World Health Organization. WHO child growth standards. Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for- age: methods and development. Geneva: World Health Organization; 2006. NLM classification: WS 103.


Refbacks

  • There are currently no refbacks.