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Revista Pan-Amazônica de Saúde

Print version ISSN 2176-6215On-line version ISSN 2176-6223

Rev Pan-Amaz Saude vol.1 no.3 Ananindeua Sept. 2010 



Dubin-Johnson syndrome: an important cause of obstructive jaundice in children



Maria Cleonice Aguiar JustinoI; Eliana Canen Pinto SoaresII; Cláudio Sérgio Carvalho de AmorimI

IInstituto de Ciências da Saúde, Universidade Federal do Pará, Belém, Pará, Brasil
IIFundação Santa Casa de Misericórdia do Pará, Belém, Pará, Brasil

Endereço para correspondência
Dirección para correspondencia


Original Title: Síndrome Dubin-Johnson: importante causa de icterícia colestática na infância. Translated by: American Journal Experts




The Dubin-Johnson syndrome is clinically characterized by recurrent episodes of benign and familial obstructive jaundice. It is identified by the presence of melanic pigment in the hepatocytes. The authors report a case of Dubin-Johnson syndrome in a child with jaundice and hepatosplenomegaly, whose diagnosis was confirmed by the presence of dark brown pigment on microscopy of liver biopsy. They suggest the suspicion of this syndrome in cases of fluctuating obstructive jaundice in children.

Keywords: Cholestasis; Jaundice; Jaundice, Chronic Idiopathic.




In 1954, the first descriptions of benign and familial jaundice with concurrent plasmatic hyperbilirubinemia at the expense of the direct fraction were described, characterized by the deposition of characteristic melanic pigment in hepatic cells1. Dubin-Johnson syndrome is a rare, genetically-determined pathology of autosomal recessive inheritance, thus favored by co-sanguinity. Jaundice evolves in spurts, which are frequently precipitated by fatigue, string emotion, physical exercise or interspersed infections, and is often followed by discrete hepatomegaly and choluria2,3,4.

In this syndrome, jaundice begins in infancy, at around two years of age, although it can also occur infrequently during the neonatal period4. The onset of symptoms can be severe and accompanied by fever, similar to a viral hepatitis5,3. There are no haematological signs attributed to hemolyses; hyperbilirubinemia occurs intermittently, with a predominance of the direct fraction, and the various liver function tests show normal values5,3. In puberty, the symptoms include jaundice, in 100% of the cases,  abdominal   pain,   especially  in  the   right hypochondrium, hepatomegaly, weakness, anorexia, choluria and fecal hipocholia1. Some patients have changes in the urinary excretion of coproporphyrins, such as the reduction of coproporphyrin III and a relative increase in the isomer I. These changes may be found to different degrees in family members.6

The syndrome occurs due to the defective expression of the MRP2 gene, an ATP-dependent canalicular membrane transporter7,8,9. The diagnosis is established by performing an oral cholecystography, a bromsulphalein test and a liver biopsy, associated with the clinical frame5,3,4.

A liver biopsy is the gold standard test for diagnosing the syndrome. It shows the presence of granular brown pigment in centrilobular hepatocyte lysosomes10,11.

In the literature, most reported cases involve young adults1,5,4,11, and, in reports involving children, there is usually a history of cholestatic jaundice of spontaneous remission in the neonatal period without an established diagnosis2,12,3,13,9,14.




Patient A.M.A. was female, two years and eight months of age, parda (brown-skinned), native and resident of the municipality of Augusto Corrêa in northeastern Pará State. The patient was admitted to the pediatric ward, sick for eight months, with symptoms of abdominal distension and intermittent episodes of fever, associated with cutaneous-mucosal pallor and fluctuating jaundice. The child was born to consanguineous parents and had a history of three episodes of malaria over the past eight months. She was treated in her hometown. There were no previous reports of jaundice.


Jaundice, mucocutaneous pallor and malnutrition were present. The abdomen was distended, normotensive, painful to superficial and deep palpation in the right upper quadrant, with the liver palpable 7 cm from the right costal margin and the spleen palpable 11 cm from the left costal margin.


The total bilirubin was 3.2 mg/dL, including 2.5 mg/dL direct bilirubin. Hemoglobin and protein electrophoresis values were within the normal ranges. The serology was negative for viral hepatitis, toxoplasmosis, syphilis, rubella, herpes, cytomegalovirus, HIV and visceral leishmaniasis. A plasmodium search was negative, and the myelogram presented no alterations.

The abdominal ultrasound revealed a hepatosplenomegaly with homogenous echotexture and no other abnormalities. A liver biopsy by light microscopy revealed the preserved architecture of the organ and hepatocytes with cytoplasmic deposits of fine, dark brown, granular pigment, distributed throughout the lobe. The deposits were Perls-negative and PAS-positive, consistent with Dubin-Johnson syndrome (Figure 1). No oral cholecystography exams, bromsulphalein test or mutation research by molecular biology were conducted, due to technical difficulties.




The patient had spontaneous resolution of the jaundice, with a slow regression of hepatosplenomegaly. After 25 days of hospitalization, the patient was discharged and referred to ambulatory care.



Dubin-Johnson syndrome is a rare disorder of genetic transmission, whose molecular basis is a defective gene that encodes the MRP28 organic anion transporter protein. Despite its genetic nature, there are reported cases with no family history of the disease6. In the present study, the patient was born to consanguineous parents and did not report any family history of symptoms consistent with the syndrome.

The onset of symptoms at two years and eight months of age was consistent with the age group described in the literature regarding the emergence of jaundice. It is likely that Plasmodium infections, which cause malaria, have contributed to the manifestation of the Dubin-Johnson syndrome due to the significant hemolysis presented by this infection.

Discrete hepatomegaly is one of the symptoms of the syndrome, and there are no reports of associated splenomegaly. The marked hepatosplenomegaly found in the patient can be attributed to repeated episodes of malaria that occurred in the months before her hospitalization, since such involvement is part of the disease framework in childhood15.



Although Dubin-Johnson syndrome is a rare disease, it is extremely important to include it in the diagnostic investigation of cases of floating jaundice in childhood. The prognosis is favorable, its course is benign, and no treatment is required. Therefore, establishing the correct diagnosis is important to prevent future unnecessary procedures. The carriers of the syndrome are later during adulthood guided not to use oral contraceptives, which can compete with the hepatocyte secretion of organic anions.



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11 Sobaniec-Lotwska ME, Lebensztejn DM. Ultrastructure of Kupffer cells and hepatocytes in the Dubin-Johnson syndrome: a case report. World J Gastroenterol. 2006 Feb;12(6):987-9.

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15 Amaral CN, Albuquerque YD, Pinto AYN, Souza JM. A importância do perfil clínico-laboratorial no diagnóstico diferencial entre malária e hepatite aguda viral. J Pediatr (Rio J). 2003;79(5):429-34.         [ Links ]



Correspondência / Correspondence / Correspondencia:
Serviço de Pediatria,
Instituto de Ciências da Saúde,
Universidade Federal do Pará
Praça Camilo Salgado, 01.
Bairro: Umarizal

Recebido em / Received / Recibido en: 29/7/2010
Aceito em / Accepted / Aceito en: 28/9/2010