ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 26 of 44
JMBS 2019, 4(2): 173–180
Clinical Medicine

The Role of Genetic and Medical-social Factors in the Course of Cystic Fibrosis. Clinical Cases

Senatorova G. S. 1, Tel'nova L. G. 1, Chernenko L. N. 1, Polyakov V. V. 2, Bashkirova N. V. 3, Strelkova M. I. 1

Cystic fibrosis is a life-shortening, multisystem genetic disease (the most common lethal genetic disease in white population). Cystic fibrosis is a hereditary autosomal recessive disease with lesions of the exocrine glands. Its frequency ranges from 1: 8000 to 1: 2000, and life expectancy is from 10 to 40 years in developed countries. The reason for cystic fibrosis is the numerous mutations in the cystic fibrosis gene, which causes the clinical course of the disease from atypical subclinical forms to severe cystic fibrosis. Since the 1930s, the development and use of an arsenal of symptomatic treatments and extensive prophylactic daily treatment regimens have extended the cystic fibrosis median predicted survival from just a few months following diagnosis to 38 years of age. The discovery of the mutated cystic fibrosis gene (cystic fibrosis transmembrane conductance regulator) in 1989, and the function of wild-type cystic fibrosis transmembrane conductance regulator protein in 1992 established the underlying pathophysiology present in cystic fibrosis epithelial tissues, including that of the sweat gland, the pancreas, the airway, and the intestine. It is now recognized that interventions targeting the underlying cystic fibrosis transmembrane conductance regulator defect across body systems have the potential to improve outcomes throughout life for persons with cystic fibrosis. The reason for cystic fibrosis is the numerous mutations in the cystic fibrosis gene, which causes the clinical course of the disease from atypical subclinical forms to severe cystic fibrosis. Results and discussion. More than 2000 mutations and 200 polymorphisms in the cystic fibrosis gene were described; its mutations were divided into 6 classes. Class I mutations result in no functional cystic fibrosis transmembrane conductance regulator protein being produced because of absent or defective protein biosynthesis. Class II mutations result in protein variants, which are improperly processed or transported to the apical cell membrane. For example, the most common and best characterized cystic fibrosis transmembrane conductance regulator mutation, F508del, is a class II mutation. One copy of F508del is present in 70% of the affected population, and 2 copies are present in approximately 50%. Class III mutations affect cystic fibrosis transmembrane conductance regulator activation and hinder chloride movement through channels at the cell surface. For example, G551D is a class III gating mutation targeted by the medication invocator, which improves chloride conductance in individuals with Cystic fibrosis with at least one copy of this mutation. Class IV mutations result in defects that produce a normal or diminished amount of cystic fibrosis transmembrane conductance regulator with decreased function at the apical epithelial cell membrane. Class V mutations result from decreased amounts of fully active cystic fibrosis transmembrane conductance regulator. Class VI mutation is characterized by diminished stability of a fully processed and functional cystic fibrosis transmembrane conductance regulator at the cell surface and often results in the truncation of cystic fibrosis transmembrane conductance regulator toward the carboxyl terminus. The disease results from 2 cystic fibrosis transmembrane conductance regulator mutations. However, they need not be from the same class. The amount of functional cystic fibrosis transmembrane conductance regulator present at the cell surface, which is determined by genotype, partially accounts for the wide spectrum of cystic fibrosis phenotypes and, to some extent, correlates with the degree of organ involvement and disease severity. Class I, II, and III mutations are typically associated with early involvement of respiratory and digestive manifestations (chronic cough, recurrent sinopulmonary infections, and exocrine pancreatic insufficiency). Class IV and V mutations are generally associated with milder or later-onset lung disease and exocrine pancreatic sufficiency. Conclusion. Observations of two clinical observations of children with "severe" and "mild" cystic fibrosis events (cystic fibrosis case with an early manifestation of diabetes mellitus in an 8-year-old child (according to literature, diabetes mellitus in patients under 10 years of age is extremely rare), and case of mild pulmonary cystic fibrosis on the background of a violation of the exchange metabolism of sulfur-containing amino acids, hyperhomocysteinemia).

Keywords: cystic fibrosis, current, children, gene mutations

Full text: PDF (Ukr) 225K

  1. Castellani C, Duff AJA, Bell SC, Heijerman HGM, Munck A, Ratjen F, et al. ECFS best practice guidelines: the 2018 revision. Journal of Cystic Fibrosis. 2018 March; 17(2): 153–78.
  2. de Groot, H, Mulder WM. Clinical practice: drug desensitization in children. Eur J Pediatr. 2010; 169(11): 1305–9.
  3. Elborn JS, Bell SC, Madge SL, Burgel PR, Castellani C, Conway S, et al. Report of the European Respiratory Society. European Cystic Fibrosis Society task force on the care of adults withcystic fibrosis. Eur Respir J. 2016; 47(2): 420–8.
  4. Farrell PM, White TB, Ren SL, Hempstead SE, Accurso F, Derichs N, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis. Foundation. Journal of Pediatrics. 2017; 181: 4-15.
  5. Floto RA, Olivier KN, Saiman L, Daley CL, Herrmann, JL, Nick JA, et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. Thorax. 2016; 71(Suppl 1): 88–90.
  6. Montgomery GS, Howenstine M. Cystic Fibrosis. Pediatrics in Review. 2009 Aug; 30(8): 302-11.
  7. Hofer M, Schmid C, Benden C, Speich R, Inci I, Weder W, et al. Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation. J Cyst Fibros. 2012; 11: 131–6.
  8. Madge S, Bell SC, Burgel P, De Rijcke K, Blasi F, Elborn JS. Limitations to providing adult cystic fibrosis care in Europe: results of a care centre survey. J Cyst Fibros. 2017; 16: 85–8.
  9. Ooi CY, Durie PR. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012; 11(5): 355–62.
  10. Plant BJ, Goss CH, Plant WD, Bell SC. Management of comorbidities in older patients with cystic fibrosis. Lancet Respir Med. 2013; 1(2): 164–74.
  11. Sadler MD, Crotty P, Fatovich L, Wilson S, Rabin HR, Myers RP. Non-invasive methods, including transient elastography, for the detection of liver disease in adults with cystic fibrosis. Can J Gastroenterol Hepatol. 2015; 29(3): 139–44.
  12. Sands D, Repetto T, Dupont LJ, Korzeniewska-Eksterowicz A, Catastini P, Madge S. End of life care for patients with cystic fibrosis. J Cyst Fibros. 2011; 10(Suppl 2): S37–44.
  13. Smith BA, Georgiopoulos AM, Quittner AL. Maintaining mental health and function for the long run in cystic fibrosis. Pediatr Pulmonol. 2016; 51: S71–S78.
  14. Senatorova AS, Chernenko LN, Muratov GR, Bashkirova NV, Yanovskaya AA. Tipichnichnye i atipichnye formy mukovistsidoza u detey. Dityachiy likar. 2014; 2(31): 10–8. [Russian]
  15. Kapranov NI, Kashirskaya NYu. Mukovistsidoz. M: Medpraktika; 2014. 67 p. [Russian]
  16. Kondyurina EG, Zelenskaya VV, Bryleva KM, Imegenov AV. Sochetanie mukovistsidoza i sakharnogo diabeta 1 tipa u rebenka rannego vozrasta. Vestnik molodogo uchenogo. 2014; 1-2: 47-50. [Russian]
  17. Natsionalnyy konsensus «Mukovistsidoz: opredelenie, diagnosticheskie kriterii, terapiya». Koordinatory: EI Kondrateva, IYu Kashirskaya, NI Kapranov. M; 2016. p. 148-55. [Russian]
  18. Senatorova AS, Chernenko LN, Shipko AF, Omelchenko EV, Telnova LG, Uryvaeva MK, et al. Mukovistsidoz u detey – problemy diagnostiki. Zhurnal im NA Dzhavakhishvili «Eksperimentalnaya i klinicheskaya meditsina». 2017; 2: 12-7. [Russian]
  19. Senatorova AS. Slozhnyy patsient v pediatrii. Kniga 2. Monografiya. Pod redaktsiey prof AS Senatorovoy. Kharkov; 2016. p. 52-70. [Russian]