Yenidoğan ve süt çocukluğunda kolestaz

Yıl 2012, Cilt: 47 Sayı: 1, 1 - 7, 01.03.2012

Fügen Çullu Çokuğraş Ömer Faruk Beşer

https://doi.org/10.4274/tpa.1547

Öz

Yenidoğan ve süt çocukluğu döneminde kolestatik karaciğer hastalıklarında buna neden olabilecek hastalığın ortaya koyulması önemlidir. Kolestaz, direkt bilirübinin total bilirübin miktarının %20’sinden fazla olmasıdır. Özellikle safra yolları atrezisi, tirozinemi, galaktozemi gibi hastalıklarda erken tanı, ileriye dönük kalıcı hasarların önlenmesi ve erken tedaviden fayda görülmesi açısından önemlidir. Dolayısı ile iki haftayı geçmiş sarılığı olan tüm yenidoğanlarda bilirübin, total, direkt, indirekt olarak bakılmalıdır; total bilürübinin %20’si direkt bilirübin ise karaciğer ile ilgili bozukluklar irdelenmelidir. Bu derlemede kolestatik karaciğer hastalıklarında nedenin ortaya koyulması açısından klinik ve laboratuvar olarak nelere dikkat edilmesi gerekir, bunu göstermeyi amaçladık.

Anahtar Kelimeler

Direkt hiperbilirübinemi, kolestaz, safra yolları atrezis

Cholestasis in newborn and infancy period

Öz

Dear Editor Isotretinoin is a synthetic vitamin A derivative which is used for treatment of nodulocystic and severe acne It is a teratogenic factor which can lead to intrauterine death and congenital anomalies in humans and the clinical picture it causes is named isotretinoin embryopathy 1 A three months old infant who was born from a mother who used isotretinoin during her first month of pregnancy without realising that she was pregnant is presented in this article to emphasize that this drug should definetely not be started in women who plan a pregnancy A three month old male presented to our clinic with a prediagnosis of multiple anomalies because of congenital cleft palate and low set and malformed ears When maternal history of the baby who was born from the first pregnancy of a 19 year old mother with a birth weight of 2400 g was deepened in terms of the infant rsquo;s malformations it was learned that the mother used isotretinoin at a dose of 0 5 mg kg day until the fourth week when she realized that she was pregnant because of widespread acnes on her face The mother discontinued the drug on the fourth week when she realized that she was pregnant Physical examination revealed the following findings: height 54 cm 3 10th percentile body weight 3800 g 10 25th percentile and head circumference 38 cm 25 50th percentile Ptosis was present in the left eyelid Picture 1 Low set malformed auricle micrognatia Picture 2 and cleft palate Picture 3 were observed A 2 6 systolic murmur was heard in the mesocardiac area Laboratory examinations revealed that complete blood count biochemical tests and urinalysis were within normal limits Patent foramen ovale was found on echocardiographic examination Hydrocephaly Dandy Walker malformation and cerebellar vermis hypoplasia Picture 4 were found on cranial magnetic resonance MR imaging The patient is still being followed up and treated in our clinic Isotretinoin embryopathy which is caused by isotretinoin is manifested by auricle anomalies cleft palate micrognatia cardiac defects aortic arcus malformations and central nervous system anomalies 1 2 Our patient had findings compatible with isotretinoin embryopathy including auricle anomalies ptosis cleft palate micrognatia patent foramen ovale hydrocephaly Dandy Walker malformation and cerebellar vermis hypoplasia In a study performed by Lammer et al 1 in 1985 21 cases exposed to isotretinoin were examined and craniofacial anomaly was found in 17 subjects cardiac anomaly was found in 12 subjects central nervous system anomalies were found in 18 subjects and thymus development anomalies were found in 7 subjects In vivo and in vitro studies have shown that isotretinoin affects the development of cranial neural crest cells 3 Pregnancy test should definetely be performed in women in whom isotretinoin treatment will be started and if the test is negative treatment should be only started after obtaining informed consent The treatment should be limited to one month and the drug should be discontinued at the end of one month However it was reported that it could lead to ear anomalies despite discontinuation of the drug one month before pregnancy 4 6 A dose of 0 5 1 5 mg kg day isotretinoin has been reported to be enough for teratogenicity 7 Our patient was exposed to 0 5 mg kg day isotretinoin In a case reported from our country ldquo;anotia rdquo; and Taussing Bing malformation were described 8 When the history and physical examination findings of the anomalies of our patient are considered it is clear that it is caused by isotretinoin Conclusively we believe that the best approach would be not to start drugs including isotretionin which have teratogenic effect in pregnant women or in women with child bearing potential Habip Almiş Yunus Emre Kum Yeşim Önal Cengiz Yakıncı İnönü University Medical Faculty Department of Pediatrics Malatya Turkey References 1 Lammer EJ Chen DT Hoar RM et al Retinoic acid embryopathy N Engl J Med 1985;313:837 41 2 Hersh JH Danhauer DE Hand ME Weisskopf B Retinoic acid embryopathy: timing of exposure and effects on fetal development JAMA 1985;254:909 ndash;10 3 Webster WS Johnston MC Lammer EJ Sulik KK Isotretinoin embryopathy and the cranial neural crest: an in vivo and in vitro study J Craniofac Genet Dev Biol 1986;6:211 ndash;22 4 Nulman I Berkovitch M Klein J et al Steady state pharmacokinetics of isotretinoin and its 4 oxo metabolite: implications for fetal safety J Clin Pharmacol 1998;38:926 ndash;30 5 Lee SM Kim HM Lee JS et al A case of suspected isotretinoin induced malformation in a baby of a mother who became pregnant one month after discontinuation of the drug Yonsei Med J 2009;50:445 ndash;7 6 Johnson BA Nunley JR Use of systemic agents in the treatment of acne vulgaris Am Fam Physician 2000;62:1823 30 7 Jones KL Smith rsquo;s recognizable pattern of human malformation 6th ed Philadelphia: Elsevier Saunders 2006: 660 1 8 Ceviz N Özkan B Eren S Ors R Olguntürk R A case of isotretinoin embryopathy with bilateral anotia and Taussig Bing malformation Turk J Pediatr 2000;42:239 41

Anahtar Kelimeler

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Kaynakça

• American Academy of Pediatrics Subcommittee on hyperbilirubinemia. Clinical practice guideline management of hiperbilirubinemia in the newborn infant 35 or more weeks of gestation (editorial). Pediatrics ; 114: 297-316. Kasai M, Watanabe I, Ohi R. Follow-up studies of long term survivors after hepatic portoenterostomy for ‘noncorrectible’ biliary atresia. J Pediatr Surg 1975; 10: 173-82.
• De Bruyne R, Van Biervliet S, Vande Velde S, Van Winckel M. Clinical practice neonatal cholestasis. Eur J Pediatr 2011; 170: 279-84.
• Mowat AP, Psacharopoulos HT, Williams R. Extrahepatic biliary atresia versus neonatal hepatitis: review of 137 prospectively investigated infants. Arch Dis Child 1976; 6: 471-85.
• Alagille D. Cholestatic in the first three months of life. Prog Liver Dis ; 6: 471-85. Dehghani SM, Haghighat M, Imanieh MH, Geramizadeh B. Comparison of different diagnostic methods in infants with cholestasis. World J Gastroenterol 2006; 12(36): 5893-6.
• Humphrey TM, Stringer MD. Biliary atresia: US diagnosis. Radiology ; 244(3): 845-51. McKiernan PJ, Baker AJ, Kelly DA. The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 2000; 355(9197): 25-9.
• Santos JL, Kieling CO, Meurer L, et al. The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenterostomy is associated with the postoperative prognosis. J Pediatr Surg 2009;44: 695-701.
• Yuan-Tsong Chen. Defects in galactose metabolism. In: Behrman RE, Kliegman RM, Jenson HB, (eds). Nelson textbook of pediatrics. th ed. Pennsylvania: Saunders, 2004: 475-6.
• Bosch AM, Grootenhuis MA, Bakker HD, Heijmans HS, Wijburg FA, Last BF. Living with classical galactosemia: health-related quality of life consequences. Pediatrics 2004; 113: 423-8.
• Phaneuf D, Lambert M, Laframboise R, Mitchell G, Lettre F, Tanguay RM. Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient. J Clin Invest 1992; 90: 1185-92.
• Mitchell GA, Lambert M, Tanguay RM. Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly W, Valle D (eds). The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill, 1995; 1077-106.
• Sander J, Janzen N, Peter M, et al. Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. Clin Chem 2006; 52: 482-7.
• Ruiz M, Sanchez-Valverde F, Rolman J, Gomez L. Dietary treatment of inborn errors of metabolism diseases. 2ed. Madrid: Drug Farma, : 111-313. Santra S, Baumann U. Experiencia com nitisinona para el tratamiento farmacológico de la tirosinemia hereditaria tipo 1. Expert Opin Pharmacother 2008; 9: 1229-36.
• Brantly M, Nukiwa T, Crystal G. Molecular basis of alpha-1-antitrypsin deficiency. Am J Med 1982;84: 12-31.
• Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequenties. Orphanet J Rare Dis 2008; 3: 16-7.
• Hutchinson DCS. Natural history of alpha-1-protease inhibitor deficiency. Am J Med 1988; 84: 3-12.
• Brantly M. Efficient and accurate approaches to the laboratory diagnosis of alpha 1-antitrypsin deficiency: the promise of early diagnosis and intervention. Clin Chem 2006; 52: 2180-1. de Serres FJ. Worlwide racial and ethnic distribution of alpha-antitrypsin deficiency. Summary of an analysis of published genetic epidemiologic surveys. Chest 2002; 122: 1818-29.
• Moskowitz SM, Gibson RL, Effmann EL. Cystic fibrosis lung disease: genetic influences, microbial interactions, and radiological assessment. Pediatr Radiol 2005; 35: 739-57.
• Zielenski J, Patrizio P, Corey M, et al. CFTR gene variant for patients with congenital absence of vas deferens. Am J Hum Genet 1995; 57: 958-60.
• Blackman SM, Deering-Brose R, McWilliams R, et al. Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis. Gastroenterology 2006; 131: 1030-9.
• Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998; 132: 589-95.
• De Boeck K, Weren M, Proesmans M, Kerem E. Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics 2005; 115: 463-9.
• Colombo C, Russo MC, Zazzeron L, Romano G. Liver disease in cystic fibrosis. J Pediatr Gastroenterol Nutr 2006; 43(Supll 1): 49-55.
• Cystic Fibrosis Foundation. CFF Patient Registry. Bethesda, Maryland: 2005.
• Fridell JA, Bond GJ, Mazariegos GV, et al. Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center’s experience. J Pediatr Surg 2003; 38: 1152-6.
• Horslen S, Sweet S, Gish RG, Shepherd R. Model for end-stage liver disease (MELD) exception for cystic fibrosis. Liver Transpl 2006; 12: 98-9.
• Jacquemin E. Progressive familial intrahepatic cholestasis. J Gasroenterol Hepatol 1999; 14: 594-9.
• Schneider BL. Genetic cholestasis syndromes. J Pediatr Gastroenterol Nutr 1999; 28: 124-31.
• Bull LN, van Eijk MJT, Pawlikowska L, et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet ; 18: 219-23. de Vree JM, Jacquemin E, Sturm E, et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci USA 1998; 95: 282-7. van Ooteghem NA, Klomp LW, van Berge-Henegouwen GP, Houwen
• RH. Benign recurrent intrahepatic cholestasis progressing to progressive familial intrahepatic cholestasis: low GGT cholestasis is a clinical continum. J Hepatol 2002; 36: 439-43.
• Brenard R, Geubel AP, Benhamou JP. Benign recurrent intrahepatic cholestasis: a report of 26 cases. J Clin Gastroenterol 1989; 11: 546-51.
• Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’. J Hepatol 2001; 35: 134-46.
• Deleunay JL, Durand-Schneider AM, Delautier D, et al. A missense mutation in ABCB4 gene involved in progressiv familial intrahepatic cholestasis type 3 leads to a folding defect that can be rescued by low temperature. Hepatology 2009; 49: 1218-27.
• Jacquemin E, Setchell KD, O’Connel NC, et al. A new cause of progressive intrahepatic cholestasis. 3β-hydroxy-C27-steroid dehydrogenase/isomerase deficiency. J Pediatr 1994; 125: 379-84.
• Rebhandl W, Felberbauer FX, Huber WD, et al. Progressive familial intrahepatic cholestasis (Byler disease): current genetics and therapy. Klin Padiatr 2000; 212: 64-70.
• Ismail H, Kalicinski P, Markiewicz M, et al. Treatment of progressive familial intrahepatic cholestasis: liver transplantation or partial external biliary diversion. Pediatr Transplant 1999; 3: 219-24.
• Oda T, Elkahloun AG, Pike BL, et al. Mutations in the human jagged 1 gene are responsible for Alagille syndrome. Nat Genet 1997; 16: 235-42.
• McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Allagile syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 2006; 79: 169-73.
• Alagille D, Odièvre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformation, retarded physical, mental and sexual development and cardiac murmur. J Pediatr 1975; 86: 63-71.
• D’Apolito O, Pianese P, Salvia G, et al. Plasma levels of conjugated bile acids in newborns after a short period of parenteral nutrition. J Parenter Enteral Nutr 2010; 34: 538-41.
• Chirico G, Barbieri F, Chirico C. Antibiotics for the newborn. J Matern Neonatal Med 2009; 22: 46-9.
• Kobayashi K, Sinasac DS, Iijima M, et al. The gene mutated in adult- onset type II citrullinaemia encodes a putative mithochondrial carrier protein. Nat Genet 1999; 22: 159-63.
• Tazawa Y, Kobayashi K, Abuwaka D, et al. Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. Mol Genet Metab 2004; 83: 213-9.
• Fraile PQ, Hernandez EM, Martinez de Aragon A, et al. Niemann-Pick type C disease: from neonatal cholestasis to neurological degeneration. Different phenotypes. An Pediatr (Barc) 2001; 73: 257-63.