Journal Mobile Options
Table of Contents
Vol. 64, No. 3, 2006
Issue release date: November 2007
Section title: Paper
Ann Nestlé [Ger] 2006;64:121–132
(DOI:10.1159/000107641)

Diagnostische Verfahren, klinische Merkmale und Beratung bei Mukoviszidose (cystischer Fibrose, CF)

De Boeck K.
Department of Pediatrics, University of Leuven, Leuven, Belgium
email Corresponding Author

Abstract

Bei den meisten Patienten, bei denen schliesslich eine Mukoviszidose (cystische Fibrose, CF) diagnostiziert wird, treten in den ersten Lebensmonaten klassische Symptome auf, wie z.B. Mekonium-Ileus, Gedeihstörungen sowie rezidivierender oder persistierender Husten. Die Krankheitssymptome treten offen zutage, sind progressiv und betreffen diverse Organsysteme. Standardtest bei der Diagnose die- ser Erkrankung ist der Schweisstest. Eine Chloridkonzentration von >60 mmol/l bestätigt den klinischen Verdacht und sichert die Diagnose. Seit Entdeckung der Mutationen des CFTR (Cystische Fibrose Transmembran Regulator)-Gens ist mittlerweile klar geworden, dass das klinische Spektrum der Erkrankung breit gefächert ist. Es wurde bereits der Nachweis erbracht, dass mehrere Patientengruppen zwei CFTR-Mutationen in sich tragen, und zwar Patienten mit klassischer CF, Patienten mit weniger stark ausgeprägten Symptomen, bei denen die Erkrankung erst in der Jugend oder sogar erst im Erwachsenenalter auftritt, und Patienten mit nur einem klinischen Merkmal, z.B. rezidivierender Pankreatitis, sklerosierender Cholangitis, ‘idiopathischer’ Bronchiektasie und Infertilität. Bei den beiden letzten Kategorien spricht man von einer atypischen CF. Diese Patienten müssen wissen, dass sie nicht unter einer typischen CF leiden, aber dass sie dennoch ein gewisses Risiko für eine der Mukoviszidose ähnliche Erkrankung haben und daher von Zeit zu Zeit von Ärzten, die mit dem äusserst breitgefächerten Spektrum dieser Erkrankung vertraut sind, untersucht und überwacht werden müssen. Die am häufigsten bei Patienten mit typischer CF auftretenden Symptome sind chronisch-progressive, bakterielle Infekte und Entzündungen der oberen und unteren Atemwege, die sich zeitweilig verschlechtern. Bei 90% der Patienten liegt eine Insuffizienz der Bauchspeicheldrüse vor. Die betroffenen Männer sind nach der Pubertät zeugungsunfähig. Bei Patienten mit Mukoviszidose können Symptome und Komplikationen in den Nebenhöhlen, in der Lunge, in der Bauchspeicheldrüse, in der Leber, im Darm, im Ösophagus, in den Knochen und in den Gelenken etc. auftreten. Die komplexe Mischung möglicher Krankheitssymptome bedeutet, dass jeder Patient einzigartig ist. Mit zunehmendem Alter nimmt die Zahl der Komplikationen tendenziell zu und die körperliche Verfassung verschlechtert sich. Aufgrund der fortgeschrittenen Lungenerkrankung können sich viele Mukoviszidose-Patienten im jungen Erwachsenenalter nicht mehr sportlich betätigen und 20% leiden unter einem mit der Mukoviszidose in Zusammenhang stehenden Diabetes mellitus. Bei der typischen CF handelt es sich um eine lebensverkürzende Erkrankung und die mittlere Überlebensdauer beträgt derzeit selbst bei intensivster Behandlung und Beobachtung nur ungefähr 34 Jahre. Auf den Patienten und ihren Familien lastet daher ein enormer psychischer Druck. Beratung ist somit von äusserster Wichtigkeit und sehr komplex.

© 2006 Nestec Ltd., Vevey/S. Karger AG, Basel


  

Schlüsselwörter

  • Cystische Fibrose
  • Schweisstest
  • CFTR-Mutation
  • Messung der nasalen Potenzialdifferenz
  • Salzverlust-Syndrom
  • Pseudomonas aeruginosa
  • Pankreasinsuffizienz
  • Infertilität

References

  1. Report of a Joint Meeting of WHO/ECFTN/ICF/(M)A/ECFS: The Molecular Genetic Epidemiology of Cystic Fibrosis. Geneva, WHO, 2006. http//:www.who.int/genomics/publications/en/
  2. Boucher RC: Regulation of airway surface liquid volume by human airway epithelia. Pflugers Arch 2003;445:495–498.
  3. Rosenstein BJ: Diagnostic methods; in Hodson M, Geddes D (eds): Cystic Fibrosis. London, Arnold, 2006, vol 2, pp 177–188.
  4. Mushtaq I, Wright VM, Drake DP, et al: Meconium ileus secondary to cystic fibrosis. The East London experience. Pediatr Surg Int 1998;13:365–369.
  5. Shapira R, Hadzic N, Francavilla R, et al: Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child 1999;81:125–128.
  6. Lai HJ, Cheng Y, Farrell PM: The survival advantage of patients with cystic fibrosis diagnosed through neonatal screening: evidence from the United States Cystic Fibrosis Foundation registry data. J Pediatr 2005;147:S57–S63.
  7. Waters DL, Dorney SF, Gaskin KJ, et al: Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. N Engl J Med 1990;322:303–308.
  8. Abman SH, Accurso FJ, Butler-Simon N, et al: Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr 1988;113:826–830.
  9. Sojo A, Rodriguez-Soriano J, Vitoria JC, et al: Chloride deficiency as a presentation or complication of cystic fibrosis. Eur J Pediatr 1994;153:825–828.
  10. Chillon M, Casals T, Mercier B, et al: Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332:1475–1480.
  11. Muniz AE, Bartle S, Foster R: Edema, anemia, hypoproteinemia, and acrodermatitis enteropathica: an uncommon initial presentation of cystic fibrosis. Pediatr Emerg Care 2004;20:112–114.
  12. Grosse SD, Boyle CA, Botkin JR, et al: Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 2004;53:1–36.

    External Resources

  13. Scotet V, de Braekeleer M, Roussey M, et al: Neonatal screening for cystic fibrosis in Brittany, France: assessment of 10 years’ experience and impact on prenatal diagnosis. Lancet 2000;356:789–794.
  14. Gibson LE, Cooke RE: A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 1959;23:545–549.
  15. Orenstein DM, Winnie GB, Altman H: Cystic fibrosis: a 2002 update. J Pediatr 2002;140:156–164.
  16. LeGrys VA: Sweat testing for the diagnosis of cystic fibrosis: practical considerations. J Pediatr 1996;129:892–897.
  17. Guidelines for the performance of the sweat test for the investigation of cystic fibrosis in the UK. Report from the multi-disciplinary working group. July 2002 (http//:www.acb.org.uk).
  18. Di Sant’Agnese PA, Darling RC, Perera GA, Shea E: Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas; clinical significance and relationship to the disease. Pediatrics 1953;12:549–563.

    External Resources

  19. Kirk JM, Keston M, McIntosh I, Essa S: Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases. Ann Clin Biochem 1992;29:145–152.
  20. Lebecque P, Leal T, De Boeck C, et al: Mutations of the cystic fibrosis gene and intermediate sweat chloride levels in children. Am J Respir Crit Care Med 2002;165:757–761.
  21. National Committee for Clinical Laboratory Standards (NCCLS): Sweat Testing: Sample Collection and Quantitative Analysis. Approved guideline C34-A2. Wayne, NCCLS, 2006.
  22. Highsmith WE, Burch LH, Zhou Z, et al: A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N Engl J Med 1994;331:974–980.
  23. Cystic Fibrosis Genotype-Phenotype Consortium: Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993;329:1308–1313.
  24. http://genet.sickkids.on.ca/cgi-bin/WebObjects/MUTATION
  25. Schaedel C, Hjelte L, de Monestrol I, et al: Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden. Clin Genet 1999;56:318–322.
  26. Dequeker E, Cuppens H, Dodge J, et al: Recommendations for quality improvement in genetic testing for cystic fibrosis. European Concerted Action on Cystic Fibrosis. Eur J Hum Genet 2000;8(suppl 2):S2–S24.
  27. Donaldson SH, Boucher RC: Update on pathogenesis of cystic fibrosis lung disease. Curr Opin Pulm Med 2003;9:486–491.
  28. Knowles MR, Paradiso AM, Boucher RC: In vivo nasal potential difference: techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum Gene Ther 1995;6:445–455.
  29. Rosenstein BJ, Cutting GR: The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998;132:589–595.
  30. Schuler D, Sermet-Gaudelus I, Wilschanski M, et al: Basic protocol for transepithelial nasal potential difference measurements. J Cyst Fibros 2004;3(suppl 2):151–155.

    External Resources

  31. Standaert TA, Boitano L, Emerson J, et al: Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trials. Pediatr Pulmonol 2004;37:385–392.
  32. Armstrong DS, Grimwood K, Carlin JB, et al: Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med 1997;156:1197–1204.
  33. Frederiksen B, Koch C, Hoiby N: Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997;23:330–335.
  34. Corey M, Edwards L, Levison H, Knowles M: Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis. J Pediatr 1997;131:809–814.
  35. Rosenfeld M, Emerson J, Williams-Warren J, et al: Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001;139:359–365.
  36. Collinson J, Nicholson KG, Cancio E, et al: Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 1996;51:1115–1122.
  37. Corey M, McLaughlin FJ, Williams M, Levison H: A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol 1988;41:583–591.
  38. Brasfield D, Hicks G, Soong S, Tiller RE: The chest roentgenogram in cystic fibrosis: a new scoring system. Pediatrics 1979;63:24–29.
  39. Mastella G, Rainisio M, Harms HK, et al: Allergic bronchopulmonary aspergillosis in cystic fibrosis. Eur Respir J 2001;17:1052–1053.
  40. Jorissen MB, De Boeck K, Cuppens H: Genotype-phenotype correlations for the paranasal sinuses in cystic fibrosis. Am J Respir Crit Care Med 1999;159:1412–1416.
  41. De Boeck K, Weren M, Proesmans M, Kerem E: Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics 2005;115:e463–e469.
  42. Moran A, Hardin D, Rodman D, et al: Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res Clin Pract 1999;45:61–73.
  43. Mascarenhas MR: Treatment of gastrointestinal problems in cystic fibrosis. Curr Treat Options Gastroenterol 2003;6:427–441.
  44. Martens M, De Boeck K, Van Der Steen K, et al: A right lower quadrant mass in cystic fibrosis: a diagnostic challenge. Eur J Pediatr 1992;151:329–331.
  45. Sokol RJ, Durie PR: Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 1999;28(suppl 1):S1–S13.
  46. Williams SG, Evanson JE, Barrett N, et al: An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis. J Hepatol 1995;22:513–521.
  47. Heine RG, Button BM, Olinsky A, et al: Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis. Arch Dis Child 1998;78:44–48.
  48. Sinaasappel M, Stern M, Littlewood J, et al: Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros 2002;1:51–75.
  49. Roulet M, Frascarolo P, Rappaz I, Pilet M: Essential fatty acid deficiency in well nourished young cystic fibrosis patients. Eur J Pediatr 1997;156:952–956.
  50. Strandvik B, Gronowitz E, Enlund F, et al: Essential fatty acid deficiency in relation to genotype in patients with cystic fibrosis. J Pediatr 2001;139:650–655.
  51. Edenborough FP, Stableforth DE, Webb AK, et al: Outcome of pregnancy in women with cystic fibrosis. Thorax 1995;50:170–174.
  52. Conway S: Osteoporosis is cystic fibrosis. J Cyst Fibros 2003;2:161–162.
  53. Elgudin L, Kishan S, Howe D: Depression in children and adolescents with cystic fibrosis: case studies. Int J Psychiatry Med 2004;34:391–397.
  54. Kotwicki RJ, Condra L, Vermeulen L, et al: Assessing the quality of life in children with cystic fibrosis. WMJ 2001;100:50–54.
  55. De Boeck K, Wilschanski M, Castellani C, et al: Cystic fibrosis: terminology and diagnostic algorithms. Thorax 2005.
  56. Classification of cystic fibrosis and related disorders. J Cyst Fibros 2002;1:5–8.

    External Resources

  57. Richards CS, Grody WW: Prenatal screening for cystic fibrosis: past, present and future. Expert Rev Mol Diagn 2004;4:49–62.
  58. Evers-Kiebooms G, Denayer L, Cassiman JJ, Van den Berghe H: Family planning decisions after the birth of a cystic fibrosis child: the impact of prenatal diagnosis. Scand J Gastroenterol 1988;23:38–46.
  59. Mischler EH, Wilfond BS, Fost N, et al: Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling. Pediatrics 1998;102:44– 52.
  60. Clarke A: The genetic testing of children. Working Party of the Clinical Genetics Society (UK). J Med Genet 1994;31:785–797.
  61. Super M, Schwarz MJ, Malone G, et al: Active cascade testing for carriers of cystic fibrosis gene. BMJ 1994;308:1462–1467.

  

Author Contacts

Prof. Dr. K. De Boeck
Department of Pediatrics
Herestraat 49, BE–3000 Leuven (Belgium)
Tel. +32 16 343 820, Fax +32 16 343 842
E-Mail christiane.deboeck@uz.kuleuven.ac.be

  

Article Information

Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 2, Number of References : 61

  

Publication Details

Annales Nestlé (Deutsche Ausg.)

Vol. 64, No. 3, Year 2006 (Cover Date: November 2007)

ISSN: 0250–9652 (print), 1661–3740 (Online)

For additional information: http://www.karger.com/AND


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References

  1. Report of a Joint Meeting of WHO/ECFTN/ICF/(M)A/ECFS: The Molecular Genetic Epidemiology of Cystic Fibrosis. Geneva, WHO, 2006. http//:www.who.int/genomics/publications/en/
  2. Boucher RC: Regulation of airway surface liquid volume by human airway epithelia. Pflugers Arch 2003;445:495–498.
  3. Rosenstein BJ: Diagnostic methods; in Hodson M, Geddes D (eds): Cystic Fibrosis. London, Arnold, 2006, vol 2, pp 177–188.
  4. Mushtaq I, Wright VM, Drake DP, et al: Meconium ileus secondary to cystic fibrosis. The East London experience. Pediatr Surg Int 1998;13:365–369.
  5. Shapira R, Hadzic N, Francavilla R, et al: Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child 1999;81:125–128.
  6. Lai HJ, Cheng Y, Farrell PM: The survival advantage of patients with cystic fibrosis diagnosed through neonatal screening: evidence from the United States Cystic Fibrosis Foundation registry data. J Pediatr 2005;147:S57–S63.
  7. Waters DL, Dorney SF, Gaskin KJ, et al: Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. N Engl J Med 1990;322:303–308.
  8. Abman SH, Accurso FJ, Butler-Simon N, et al: Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr 1988;113:826–830.
  9. Sojo A, Rodriguez-Soriano J, Vitoria JC, et al: Chloride deficiency as a presentation or complication of cystic fibrosis. Eur J Pediatr 1994;153:825–828.
  10. Chillon M, Casals T, Mercier B, et al: Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332:1475–1480.
  11. Muniz AE, Bartle S, Foster R: Edema, anemia, hypoproteinemia, and acrodermatitis enteropathica: an uncommon initial presentation of cystic fibrosis. Pediatr Emerg Care 2004;20:112–114.
  12. Grosse SD, Boyle CA, Botkin JR, et al: Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 2004;53:1–36.

    External Resources

  13. Scotet V, de Braekeleer M, Roussey M, et al: Neonatal screening for cystic fibrosis in Brittany, France: assessment of 10 years’ experience and impact on prenatal diagnosis. Lancet 2000;356:789–794.
  14. Gibson LE, Cooke RE: A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 1959;23:545–549.
  15. Orenstein DM, Winnie GB, Altman H: Cystic fibrosis: a 2002 update. J Pediatr 2002;140:156–164.
  16. LeGrys VA: Sweat testing for the diagnosis of cystic fibrosis: practical considerations. J Pediatr 1996;129:892–897.
  17. Guidelines for the performance of the sweat test for the investigation of cystic fibrosis in the UK. Report from the multi-disciplinary working group. July 2002 (http//:www.acb.org.uk).
  18. Di Sant’Agnese PA, Darling RC, Perera GA, Shea E: Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas; clinical significance and relationship to the disease. Pediatrics 1953;12:549–563.

    External Resources

  19. Kirk JM, Keston M, McIntosh I, Essa S: Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases. Ann Clin Biochem 1992;29:145–152.
  20. Lebecque P, Leal T, De Boeck C, et al: Mutations of the cystic fibrosis gene and intermediate sweat chloride levels in children. Am J Respir Crit Care Med 2002;165:757–761.
  21. National Committee for Clinical Laboratory Standards (NCCLS): Sweat Testing: Sample Collection and Quantitative Analysis. Approved guideline C34-A2. Wayne, NCCLS, 2006.
  22. Highsmith WE, Burch LH, Zhou Z, et al: A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N Engl J Med 1994;331:974–980.
  23. Cystic Fibrosis Genotype-Phenotype Consortium: Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993;329:1308–1313.
  24. http://genet.sickkids.on.ca/cgi-bin/WebObjects/MUTATION
  25. Schaedel C, Hjelte L, de Monestrol I, et al: Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden. Clin Genet 1999;56:318–322.
  26. Dequeker E, Cuppens H, Dodge J, et al: Recommendations for quality improvement in genetic testing for cystic fibrosis. European Concerted Action on Cystic Fibrosis. Eur J Hum Genet 2000;8(suppl 2):S2–S24.
  27. Donaldson SH, Boucher RC: Update on pathogenesis of cystic fibrosis lung disease. Curr Opin Pulm Med 2003;9:486–491.
  28. Knowles MR, Paradiso AM, Boucher RC: In vivo nasal potential difference: techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum Gene Ther 1995;6:445–455.
  29. Rosenstein BJ, Cutting GR: The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998;132:589–595.
  30. Schuler D, Sermet-Gaudelus I, Wilschanski M, et al: Basic protocol for transepithelial nasal potential difference measurements. J Cyst Fibros 2004;3(suppl 2):151–155.

    External Resources

  31. Standaert TA, Boitano L, Emerson J, et al: Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trials. Pediatr Pulmonol 2004;37:385–392.
  32. Armstrong DS, Grimwood K, Carlin JB, et al: Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med 1997;156:1197–1204.
  33. Frederiksen B, Koch C, Hoiby N: Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997;23:330–335.
  34. Corey M, Edwards L, Levison H, Knowles M: Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis. J Pediatr 1997;131:809–814.
  35. Rosenfeld M, Emerson J, Williams-Warren J, et al: Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001;139:359–365.
  36. Collinson J, Nicholson KG, Cancio E, et al: Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 1996;51:1115–1122.
  37. Corey M, McLaughlin FJ, Williams M, Levison H: A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol 1988;41:583–591.
  38. Brasfield D, Hicks G, Soong S, Tiller RE: The chest roentgenogram in cystic fibrosis: a new scoring system. Pediatrics 1979;63:24–29.
  39. Mastella G, Rainisio M, Harms HK, et al: Allergic bronchopulmonary aspergillosis in cystic fibrosis. Eur Respir J 2001;17:1052–1053.
  40. Jorissen MB, De Boeck K, Cuppens H: Genotype-phenotype correlations for the paranasal sinuses in cystic fibrosis. Am J Respir Crit Care Med 1999;159:1412–1416.
  41. De Boeck K, Weren M, Proesmans M, Kerem E: Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics 2005;115:e463–e469.
  42. Moran A, Hardin D, Rodman D, et al: Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: a consensus conference report. Diabetes Res Clin Pract 1999;45:61–73.
  43. Mascarenhas MR: Treatment of gastrointestinal problems in cystic fibrosis. Curr Treat Options Gastroenterol 2003;6:427–441.
  44. Martens M, De Boeck K, Van Der Steen K, et al: A right lower quadrant mass in cystic fibrosis: a diagnostic challenge. Eur J Pediatr 1992;151:329–331.
  45. Sokol RJ, Durie PR: Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 1999;28(suppl 1):S1–S13.
  46. Williams SG, Evanson JE, Barrett N, et al: An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis. J Hepatol 1995;22:513–521.
  47. Heine RG, Button BM, Olinsky A, et al: Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis. Arch Dis Child 1998;78:44–48.
  48. Sinaasappel M, Stern M, Littlewood J, et al: Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros 2002;1:51–75.
  49. Roulet M, Frascarolo P, Rappaz I, Pilet M: Essential fatty acid deficiency in well nourished young cystic fibrosis patients. Eur J Pediatr 1997;156:952–956.
  50. Strandvik B, Gronowitz E, Enlund F, et al: Essential fatty acid deficiency in relation to genotype in patients with cystic fibrosis. J Pediatr 2001;139:650–655.
  51. Edenborough FP, Stableforth DE, Webb AK, et al: Outcome of pregnancy in women with cystic fibrosis. Thorax 1995;50:170–174.
  52. Conway S: Osteoporosis is cystic fibrosis. J Cyst Fibros 2003;2:161–162.
  53. Elgudin L, Kishan S, Howe D: Depression in children and adolescents with cystic fibrosis: case studies. Int J Psychiatry Med 2004;34:391–397.
  54. Kotwicki RJ, Condra L, Vermeulen L, et al: Assessing the quality of life in children with cystic fibrosis. WMJ 2001;100:50–54.
  55. De Boeck K, Wilschanski M, Castellani C, et al: Cystic fibrosis: terminology and diagnostic algorithms. Thorax 2005.
  56. Classification of cystic fibrosis and related disorders. J Cyst Fibros 2002;1:5–8.

    External Resources

  57. Richards CS, Grody WW: Prenatal screening for cystic fibrosis: past, present and future. Expert Rev Mol Diagn 2004;4:49–62.
  58. Evers-Kiebooms G, Denayer L, Cassiman JJ, Van den Berghe H: Family planning decisions after the birth of a cystic fibrosis child: the impact of prenatal diagnosis. Scand J Gastroenterol 1988;23:38–46.
  59. Mischler EH, Wilfond BS, Fost N, et al: Cystic fibrosis newborn screening: impact on reproductive behavior and implications for genetic counseling. Pediatrics 1998;102:44– 52.
  60. Clarke A: The genetic testing of children. Working Party of the Clinical Genetics Society (UK). J Med Genet 1994;31:785–797.
  61. Super M, Schwarz MJ, Malone G, et al: Active cascade testing for carriers of cystic fibrosis gene. BMJ 1994;308:1462–1467.