Kadim BAYAN, Yekta TÜZÜN, Mansur ÖZCAN, Şerif YILMAZ, Sezer TURGUTALP

Dubin-johnson sendromu tanılı bir olgu nedeniyle konjuge hiperbilirubinemiler

Dubin-Johnson sendromu (DJS) hafif derecede kronik konjuge hiperbilirübinemi ile karakterize nadir görülen bir hastalıktır. Bu konjenital sendromda, konjuge anyonların safra kanalikülüne itrahında bozukluk vardır. Safra asitlerinin atılımı genellikle normaldir. DJS’lu hastalarda multidrug resistans related protein (MRP-2) geninde farklı mutasyonlar tespit edilmiştir. Hastalar asemptomatik olmakla birlikte bazen müphem karın ağrısı, hafif sarılık, halsizlik gibi bünyesel semptomlar görülebilir. Ondokuz yaşında erkek hasta doğduğundan beri mevcut olan sarılık yakınması ile kliniğe yatırıldı. Hastada müphem karın ağrısı ve sarılık mevcuttu. Kaşıntı yoktu. Tam kan sayımı, protrombin zamanı ve serum tarnsaminazlar, alkalen fosfataz, safra asitleri, kolesterol ve albumin değerleri normal sınırlardaydı. Serum total bilirübin konsantrasyonu 6,5 mg/dL, direkt bilirübin konsantrasyonu 4.9 mg/dL idi. 99mTc-HIDA ile yapılan hepatobiliyer sintigrafi incelemesinde karaciğer normal olup safra kesesi ise enjeksiyondan sonra geç görüntülendi. Karaciğer biyopsisinde santral ven çevresinde yoğun pigmentasyon izlendi. Bu yazıda konjuge hiperbilirübineminin nadir nedenlerinden biri olan Dubin-Johnson sendromunu sunmayı ve herediter sarılık ayırıcı tanısını vurgulamayı amaçladık

A case with conjugated hyperbilrubinemia diagnosed as dubin johnson syndrome

Dubin-Johnson Syndrome (DJS) is a rare entity and characterized by mild, chronic, conjugated hyperbilirubinemia. The abnormality of this congenital syndrome is excretion of conjugated anions into the bile canaliculus. However, acid excretion into bile is usually normal. Different mutations in multidrug resistans related protein (MRP-2) gene were identified in patients with DJS. These patients are asymptomatic and sometimes can occur constitutional symptoms such as weakness, mild icterus and abdominal pain. A 19-years-old-male patient admitted with icterus lasting since the neonatal period. He had vague abdominal pain and icterus. Pruritus was absent. Complete blood count, prothrombin time, transaminases, alkaline phosphatase, serum levels of bile acids, cholesterol and albumin were all normal. Serum total bilirubin concentration was 6,5 mg/dL, direct bilirubin concentration was 4.9 mg/dL. Hepatobilliary scan with 99mTc-HIDA excretion showed a normal liver and the gallbladder was visualized late after dye injection. Liver biopsy showed dense pigmentation around central vein. In this report we aimed to introduce a rare condition of conjugated hyperbilirubinemia diagnosed as Dubin-Johnson Syndrome and to make a point of view to differential diagnosis in hereditary jaundice.

PDF

___

1. Dubin, in, Johnson, FB. Chronic idiopathic jaundice with unidentified pigment in liver cells; a new clinicopathologic entity with a report of 12 cases. Medicine (Baltimore) 1954; 33:155.
2. Sprinz H, Nelson RS. Persistent non-hemolytic hyperbilirubinemia associated with lipochrome-like pigment in liver cells: report of four cases. Ann Intern Med 1954; 41:952
3. Shani, M, Seligsohn, U, Gilon, E, et al. Dubin-Johnson syndrome in Israel. I. Clinical, laboratory, and genetic aspects of 101 cases. Q J Med 1970; 39:549.
4. Iyanagi T, Emi Y, Ikushiro S. Biochemical and molecular aspects of genetic disorders of bilirubin metabolism. Biochim Biophys Acta. 1998; 1407: 173-184.
5. Nishida, T, Gatmaitan, Z, Roy Chowdhury, et al. Two distinct mechanisms for bilirubin glucuronide transport by rat bile canalicular membrane vesicles. J Clin Invest 1992; 90: 2130.
6. Tsujii H, Konig J, Rost D, et al. Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Gastroenterology 1999; 117: 653.
7. Mor-Cohen R, Zivelin A, Rosenberg N, et al. Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome. J Biol Chem 2001; 276: 36923.
8. Cohen L, Lewis C, Arias IM. Pregnancy, oral contraceptives, and chronic familial jaundice with predominantly conjugated hyperbilirubinemia (Dubin-Johnson syndrome) Gastroenterology 1972; 62:1182.
9. Dittrich H, Seifert E. On the behavior of pigment and biligraffin excretion in a patient with Dubin-Johnson syndrome. Acta Hepatosplenol 1962; 9: 45.
10. Morita, M, Kihara, T. Intravenous cholecystography and metabolism of meglumine iodipamide (Biligrafin) in Dubin-Johnson syndrome. Radiology 1971; 99: 57.
11. Koskelo P, Toivonen I, Adlercreutz H. Urinary coproporphyrin isomer distribution in the Dubin-Johnson syndrome. Clin Chem 1967; 13: 1006.
12. Kondo T, Kuchiba K, Shimizu Y. Coproporphyrin isomers in Dubin-Johnson syndrome.
13. Seligsohn U, Shani M, Ramot B, et al. Hereditary deficiency of blood clotting factor VII and Dubin-Johnson syndrome in an Israeli family. Isr J Med Sci 1969; 5:1060.
14. Levanon M, Rimon S, Shani M, et al. Active and inactive factor VII in Dubin-Johnson syndrome with factor-VII deficiency, hereditary factor-VII deficiency and on coumadin administration. Br J Haematol 1972; 23:669.