Pancretic disease in cystic fibrosis and alpha 1 antitrypsin deficiency Invited Editor

Year 2009, Volume: 44 Issue: 1, - , 01.03.2009

Hamza Karabiber Mukadder Ayşe Selimoğlu

Abstract

Cystic fibrosis and alpha 1 antitrypsin deficiency are two important autosomal recessive multi organ diseases They are complex and severe diseases that involve various organs including pancreas Pancreatic disease in cystic fibrosis varies from complete loss of exocrine and endocrine functions to nearly normal pancreatic function A strong correlation between genotype and phenotype is recognized Pancreatic involvement is characterized by malabsorption of fat and protein and growth failure Fat malabsorption leads to special problems with the fat soluble vitamins Enzyme and fat soluble vitamin replacements are the milestones of the malabsorption treatment Gene therapy offers the best hope for a cure of cystic fibrosis Although an association between alpha1 antitrypsin deficiency and chronic pancreatitis has been reported in several case reports in prospective studies it has been shown that pancreatitis prevalence in patients with alpha1 antitrypsin deficiency was not different from that of healthy controls Thus it was concluded that alpha 1 antitrypsin deficiency was not related to the pathogenesis of idiopathic or hereditary chronic pancreatitis However protective role of alpha 1 antitrypsin against pancreatic auto digestion suggests that the deficiency of that protein may worsen the pancreatic disease rather than causing it Early detection and management of pancreatic insufficiency is essential to optimize health and outcomes in cystic fibrosis and alpha 1 antitrypsin deficiency patients Turk Arch Ped 2009; 44: 7 11 Key words: Alfa 1 antitripsin deficinecy cystic fibrosis pancreas

Keywords

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Kistik fibroz ve alfa 1 antitripsin eksikliğinde pankreatik tutulum Çağrılı Editör

Abstract

Kistik fibroz ve alfa 1 antitripsin eksikliği birçok sistemi tutan genetik kökenli otozomal çekinik geçişli iki önemli hastalıktır Her iki hastalığın ortak olarak etkileyebildiği organlardan birinin de pankreas olduğu bilinmektedir Kistik fibroz’da pankreatik tutulum normale yakın pankreas işlevinden endokrin ve ekzokrin işlevlerinin tamamen kaybına kadar değişen klinik tablolara yol açar Hastalığın genotipi ile fenotipi arasında yakın bir ilişki vardır Pankreas tutulumu yağ ve protein emilim bozukluğu ve büyüme geriliği ile belirgindir Yağ emilim bozukluğu sonucu yağda eriyen vitamin eksikliklerine bağlı belirtiler oluşur Emilim bozukluğu tedavisi enzimin yerine konulan ve vitamin eksikliklerinin düzeltilmesi şeklinde yapılmalıdır Gen tedavisi hastalığın tümüyle tedavisi için bir umut ışığıdır Alfa 1 antitripsin eksikliği ve kronik pankreatit birlikteliği ile ilgili birçok olgu sunumu yayınlanmış olmakla birlikte pankreatitli hastaların sağlıklı kontrollerle karşılaştırıldığı çalışmalarda alfa 1 antitripsin eksikliğinin kronik pankreatit etiolojisinde rolü olmadığı sonucuna varılmıştır Ancak alfa 1 antitripsinin pankreasın kendi kendini sindirmesini önleyen etkisi göz önüne alındığında etiolojik bir etmen olmasa da eksikliğinin pankreas hastalığını artırıcı bir rolü olduğu düşünülebilir Kistik fibroz ve alfa 1 antitripsin eksikliği olan hastalarda pankreas tutulumunun erken saptanması ve tedavisi bu hastalıklardan ölüm oranının azaltılmasına önemli katkıda bulunur Türk Ped Arş 2009; 44: 7 11 Anahtar kelimeler: Alfa 1 antitripsin eksikliği kistik fibroz pankreas

Keywords

Alfa-1 antitripsin eksikliği, kistik fibroz, pankreas

References

• Danes BS, Bearn AG. Cystic fibrosis of the pancreas. J Exp Med 1969; 129: 775-93.
• Davis P. Cystic fibrosis since 1938. Am J Respir Crit Care Med 2006; 173: 475-82.
• Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245: 1073-80.
• Gaskin KJ. Cystic fibrosis. In: Walker WA, Goulet O, Kleinman RE, Sherman PM, Shneider BL, Sanderson IR (eds). Pediatric Gastrointestinal Disease. 4th ed. Newyork: BC Decker Inc, 2004;1606-23.
• Nousia-Arvanitakis S. Cystic fibrosis and the pancreas: recent scientific advances. J Clin Gastroenterol 1999; 29: 138-42.
• Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998; 132: 589-95.
• Marino CR, Matovcik LM, Gorelick FS, Cohn SA. Localization of the cystic fibrosis transmembrane conductance regulator in pancreas. J Clin Invest 1991; 88: 712-6.
• Gaskin K, Waters D, Dorney S, Gruca M, O'Halloran M, Wilcken B. Assessment of pancreatic function in screened infants with cystic fibrosis. Pediatr Pulmonol Suppl 1991; 7: 69-71.
• Imrie J, Fagan D, Sturgess J. Quantitative evaluation of the de- velopment of the exocrine pancreas in CF and control infants. Am J Pathol 1979; 95: 697-707.
• Knowlton RG, Cohen-Haguenauer O, Van Cong N, et al. A poly- morphic DNA marker linked to cystic fibrosis is located on chro- mosome 7. Nature 1985; 318: 380-2.
• Grigorescu M, Grigorescu MD. Genetic factors in pancreatitis. Rom J Gastroenterol 2005; 14: 53-61.
• Salvatore F, Scudiero O, Castaldo G. Genotype-phenotype cor- relation in cystic fibrosis: the role of modifier genes. Am J Med Genet 2002; 111: 88-95.
• Hamosh A, Corey M. Correlation between genotype and phenoty- pe in patients with cystic fibrosis. The Cystic Fibrosis Genotype- Phenotype Consortium. N Engl J Med 1993; 329: 1308-13.
• Ferrari M, Cremonesi L. Genotype-phenotype correlation in cys- tic fibrosis patients. Ann Biol Clin 1996; 54: 235-41.
• Guy-Crotte O, Carrere J, Figarella C. Exocrine pancreatic functi- on in cystic fibrosis. Eur J Gastroenterol Hepatol 1996; 8: 755-9.
• Nousia-Arvanitakis S, Karagiozoglou-Lamboudes T, Galli-Tsino- poulou A, Augoustidou-Savopoulou P, Salem N, Stefanides A. Influence of exocrine pancreas on beta-cell function in cystic fibrosis. Hellenic J Gastroenterol 1995; 8: 136-40.
• Reisman J, Petrou C, Corey M, Stringer D, Durie P, Levison H. Hypoalbuminemia at initial examination in patients with cystic fibrosis. J Pediatr 1989; 115: 755-8.
• Lowenfels AB, Maisonneuve P. Risk factors for cancer in here- ditary pancreatitis. Med Clin North Am 2000; 84: 5565-73.
• Krysa J, Steger A. Pancreas and cystic fibrosis: The implicati- ons of increased survival in cystic fibrosis. Pancreatology 2007; 7: 447-50.
• Costa M, Potvin S, Berthiaume Y, et al. Diabetes: a major co-morbidity of cystic fibrosis. Diabetes Metab 2005; 31: 221-32.
• Alves Cde A, Aguiar RA, Alves AC, Santana MA. Diabetes mel- litus in patients with cystic fibrosis. J Bras Pneumol 2007; 33: 213-21.
• Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Mor- gan WJ. Epidemiology of cystic fibrosis-related diabetes. J Pe- diatr 2005; 146: 681-7.
• Beharry S, Ellis L, Corey M, Marcon M, Durie P. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease? J Pediatr 2002; 141: 84-90.
• Borowitz D, Baker SS, Duffy L, et al. Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis. J Pedi- atr 2004; 145: 322-6.
• Chaudry G, Navarro OM, Levine DS, Oudjhane K. Abdominal manifestations of cystic fibrosis in children. Pediatr Radiol 2006; 36: 233-40.
• Berrocal T, Pajares MP, Zubillaga AF. Pancreatic cystosis in children and young adults with cystic fibrosis: sonographic, CT, and MRI findings. AJR 2005; 184: 1305-9.
• Haber HP. Cystic fibrosis in children and young adults: findings on routine abdominal sonography. AJR 2007; 189: 89-99.
• Carroccio A, Pardo F, Montalto G, et al. Effectiveness of ente- ric-coated preparations on nutritional parameters in cystic fibro- sis: a long-term study. Digestion 1988; 41: 201-6.
• Stevens JC, Magines KM, Hollingsworth J, Heilman DK, Chong SK. Pancreatic enzyme supplementation in cystic fibrosis pati- ents before and after fibrosing colonopathy. J Pediatr Gastroen- terol Nutr 1998; 26: 80-4.
• Fitzsimmons SC, Burkhart GA, Borowitz D, et al. High dose pan- creatic enzyme supplements and fibrosing colonopathy in chil- dren with cystic fibrosis. N Engl J Med 1997; 336: 1283-9.
• Costantini D, Padoan R, Curcio L, Giunta A. The management of enzymatic therapy in cystic fibrosis patients by an individualized approach. J Pediatr Gastroenterol Nutr 1988; 7: 36-9.
• Alton EW. Gene therapy for cystic fibrosis. J Inherit Metab Dis 1995; 18: 501-7.
• Rakonczay Z Jr, Hegyi P, Hasegawa M, et al. CFTR gene trans- fer to human cystic fibrosis pancreatic duct cells using a Sendai virus vector. J Cell Physiol 2008; 214: 442-55.
• Perlmutter DH. Alpha-1-antitrypsin deficiency: diagnosis and treatment. Clin Liver Dis 2004; 8: 839-59.
• Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis 2008; 3: 16-25.
• Ioachimescu OC, Stoller JK. A review of alpha-1 antitrypsin de- ficiency. COPD 2005; 2: 263-75.
• Novis BH, Young GO, Bank S, Marks IN. Chronic pancreatitis and alpha-1-antitrypsin. Lancet 1975; 2:748-9.
• Mihas AA, Hirschowitz BI. Alpha-1 antitrypsin and chronic pan- creatitis. Lancet 1976; 2: 1032-3.
• Edmunds SEJ, Wilkinson ML. Alpha-1 antitrypsin deficiency and pancreatitis in a juvenile. Aust N Z J Med 1991; 21: 345-7.
• Rabassa AA, Schwartz MR, Ertan A. Alpha-1 antitrypsin defici- ency and chronic pancreatitis. Dig Dis Sci 1995;40:1997-2001.
• Braxel C, Versieck J, Lemey G, et al. Alpha-1 antitrypsin in pan- creatitis. Digestion 1982; 23: 93-6.
• Lankisch PG, Koop H, Winckler K, et al. Alpha-1 antitrypsin in pancreatic diseases. Digestion 1978; 18: 138-40.
• Witt H, Kage A, Luck W, Becker M. Alpha-1 antitrypsin genoty- pes in patients with chronic pancreatitis. Scand J Gastroenterol 2002; 37: 356-9.
• Etemad B, Whitcomb DC. Chronic pancreatitis: Diagnosis, clas- sification, and new genetic developments. Gastroenterology 2001; 120: 682-707.
• Apte MV, Pirola RC, Wilson JS. Individual susceptibility to alco- holic pancreatitis. J Gastroenterol Hepatol 2008; 23: 63-8.
• Sobczynska-Tomaszewska A, Bak D, Oralewska B, et al. Analy- sis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis. J Pediatr Gastroenterol Nutr 2006; 43: 299-306. 111