Abstract
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that results in abnormal viscous mucoid secretions in multiple organs and whose main clinical features are pancreatic insufficiency and chronic endobronchial infection. Although it was initially defined and diagnosed based on clinical features and sweat chloride measurement, an in vivo method of assessing CFTR function, the discovery of the CFTR gene in 1989 revealed a broad spectrum of CF phenotypes associated with specific CFTR gene mutations. In this article, we will review the indications for sweat testing, alternative techniques to diagnose CF, and the approach to patients with an ambiguous or indeterminate diagnosis of CF.
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References
Davis PB, Drumm M, Konstan MW (1996) Cystic fibrosis. Am J Respir Crit Care Med 154:1229–1256
National Newborn Screening and Genetics Resource Center (2003) National newborn screening report 2000. National Newborn Screening and Genetics Resource Center, San Antonio, TX
Andersen D (1938) Cystic fibrosis of the pandrease and its relation to celiac disease: a clinical and pathological study. Am J Dis Child 56:344–399
Di Sant'Agnese P (2001) Experiences of a pioneer researcher: discovery of the sweat electrolyte defect and the early medical history of cystic fibrosis. In: Doershuk C (ed) Cystic fibrosis in the 20th century. People, events, and progress. AM, Cleveland, OH
Gibson LE, Cooke RE (1959) A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 23:545–549
Rosenstein BJ, Cutting GR (1998) The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 132:589–595
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z et al (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073
Rowntree RK, Harris A (2003) The phenotypic consequences of CFTR mutations. Ann Hum Genet 67:471–485
Davis PB (2001) Cystic fibrosis. Pediatr Rev 22:257–264
Cystic Fibrosis Foundation (2006) Cystic fibrosis foundation patient registry. Cystic Fibrosis Foundation, Bethesda, MD
Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW et al (1998) Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95:1005–1015
Wine JJ (1999) The genesis of cystic fibrosis lung disease. J Clin Invest 103:309–312
Ratjen F (2006) Restoring airway surface liquid in cystic fibrosis. N Engl J Med 354:291–293
LeGrys VA, Yankaskas JR, Quittell LM, Marshall BC, Mogayzel PJ Jr (2007) Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr 151:85–89
NCCLS (2000) Sweat testing: sample collection and quantitative analysis: approved guideline. National Committee for Clinical Laboratory Standards, Wayne, PA Document C34-A2. Clinical Laboratory Standards Institute formerly National Committee for Clinical Laboratory Standards
Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M et al (2004) Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 53:1–36
Knowles MR, Durie PR (2002) What is cystic fibrosis? N Engl J Med 347:439–442
De Boeck K, Wilschanski M, Castellani C, Taylor C, Cuppens H, Dodge J et al (2006) Cystic fibrosis: terminology and diagnostic algorithms. Thorax 61:627–635
Zeitlin PL (1999) Novel pharmacologic therapies for cystic fibrosis. J Clin Invest 103:447–452
Donaldson SH, Boucher RC (2007) Sodium channels and cystic fibrosis. Chest 132:1631–1636
Hamosh A, FitzSimmons SC, Macek M Jr., Knowles MR, Rosenstein BJ, Cutting GR (1998) Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J Pediatr 132:255–259
Wine JJ, Kuo E, Hurlock G, Moss RB (2001) Comprehensive mutation screening in a cystic fibrosis center. Pediatrics 107:280–286
Cuppens H, Lin W, Jaspers M, Costes B, Teng H, Vankeerberghen A et al (1998) Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J Clin Invest 101:487–496
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 362:160–164
O'Sullivan BP, Zwerdling RG, Dorkin HL, Comeau AM, Parad R (2006) Early pulmonary manifestation of cystic fibrosis in children with the DeltaF508/R117H-7T genotype. Pediatrics 118:1260–1265
Ren CL (2007) Pulmonary manifestations in deltaF508/R117H. Pediatrics 119:647–648
Highsmith WE, Burch LH, Zhou Z, Olsen JC, Boat TE, Spock A et al (1994) A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N Engl J Med 331:974–980
Alton EW, Currie D, Logan-Sinclair R, Warner JO, Hodson ME, Geddes DM (1990) Nasal potential difference: a clinical diagnostic test for cystic fibrosis. Eur Respir J 3:922–926
Knowles MR, Paradiso AM, Boucher RC (1995) In vivo nasal potential difference: techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum Gene Ther 6:445–455
Sauder RA, Chesrown SE, Loughlin GM (1987) Clinical application of transepithelial potential difference measurements in cystic fibrosis. J Pediatr 111:353–358
Wagener JS, Sontag MK, Accurso FJ (2003) Newborn screening for cystic fibrosis. Curr Opin Pediatr 15:309–315
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Voter, K.Z., Ren, C.L. Diagnosis of Cystic Fibrosis. Clinic Rev Allerg Immunol 35, 100–106 (2008). https://doi.org/10.1007/s12016-008-8078-x
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DOI: https://doi.org/10.1007/s12016-008-8078-x