A Síndrome de Dubin-Johnson (SDJ) é uma condição genética e benigna (que não é grave) do fígado. Ela se caracteriza por um aumento crônico (constante) de bilirrubina (uma substância amarela) no sangue, principalmente daquele tipo que já foi processado pelo fígado. Além disso, ao examinar as células do fígado ao microscópio, observa-se um depósito de um pigmento de cor marrom-escura.
Introdução
O que você precisa saber de cara
A Síndrome de Dubin-Johnson (SDJ) é uma condição genética e benigna (que não é grave) do fígado. Ela se caracteriza por um aumento crônico (constante) de bilirrubina (uma substância amarela) no sangue, principalmente daquele tipo que já foi processado pelo fígado. Além disso, ao examinar as células do fígado ao microscópio, observa-se um depósito de um pigmento de cor marrom-escura.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 6 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 12 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal recessive.
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-
Apical cell membrane
Dubin-Johnson syndrome
Autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function.
Variantes genéticas (ClinVar)
246 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 218 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
6 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome Dubin-Johnson
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Genetically confirmed Dubin-Johnson syndrome presenting as long-standing isolated conjugated hyperbilirubinaemia.
Isolated hyperbilirubinaemia with normal liver enzymes is frequently attributed to Gilbert syndrome, but predominance of conjugated bilirubin warrants evaluation for inherited disorders of bilirubin transport. We report a genetically confirmed case of Dubin-Johnson syndrome in a young adult with a 10-year history of intermittent jaundice and persistently conjugated hyperbilirubinaemia, despite normal liver biochemistry and imaging. Extensive evaluation excluded haemolysis, viral hepatitis, autoimmune liver disease and structural biliary pathology. Targeted genetic testing identified a homozygous loss-of-function variant in the ABCC2 gene, establishing the diagnosis. The patient required no specific treatment and remained clinically stable on follow-up. This case emphasises the importance of recognising Dubin-Johnson syndrome in long-standing conjugated hyperbilirubinaemia and the role of genetic testing in avoiding unnecessary invasive investigations in this benign, non-progressive condition.
ATP-binding Cassette Transporter Defects and Their Roles in Hepatic Diseases.
ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations in particular genes encoding these transporters-including BSEP (ABCB11 gene), MDR3 (ABCB4 gene), sterolin-1 and sterolin-2 (ABCG5/8 genes), and MRP2 (ABCC2 gene)-result in a wide spectrum of liver diseases, ranging from benign conditions such as Dubin-Johnson syndrome to more severe presentations like progressive familial intrahepatic cholestasis. The severity of disease is influenced by many factors, including zygosity, mutation type, and environmental modifiers such as hormones, consanguinity, and founder effects. Homozygous and compound heterozygous mutations typically result in severe and early-onset diseases, while heterozygous single-allelic mutants generally result in milder diseases. Next-generation genetic testing has proven to have high diagnostic value and is important for prognostication. With knowledge of the underlying specific mutations, there is also potential for future targeted therapy for many severe diseases. The aim of this review is to update and discuss the hepatic diseases associated with ABC transporter mutations, the genetic and environmental effects that influence the severity of disease, typical presentations of these cholestatic hepatic diseases, diagnostic considerations, and treatment options.
Expert Consensus on the Diagnosis and Management of Inherited Hyperbilirubinemia (2025).
To support clinicians in making informed decisions regarding the diagnosis and management of inherited hyperbilirubinemia, including Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor syndrome, the Inherited and Metabolic Liver Disease Collaboration Group of the Hepatology Branch of the Chinese Medical Association convened a panel of Chinese experts in this field. This multidisciplinary consortium developed the present expert consensus by integrating the latest advances in both clinical practice and basic research.
A novel pathogenic variant for dubin-johnson syndrome in a case of hyperbilirubinemia and metabolic associated fatty liver disease.
Dubin-Johnson Syndrome (DJS; OMIM 237500) is a rare autosomal recessive disorder caused by pathogenic variants in the ABCC2 gene, encoding for the multidrug resistance protein 2 (MRP2), resulting in impeded biliary excretion of bilirubin metabolites. It is typically characterized by chronic or intermittent jaundice and conjugated hyperbilirubinemia. We report the case of a 54-year-old male with hyperbilirubinemia (mostly conjugated) and hypertransaminasemia. Hypertransaminasemia was due to presence of Metabolic dysfunction-associated fatty liver disease (MASLD), while whole-genome sequencing revealed a homozygous missense variant affecting ABCC2 (c.3893G > A, p.Gly1298Asp), a previously undescribed variant likely linked to hyperbilirubinemia. It is an extremely rare genetic variant (allele frequency = 6.2 × 10-7). In silico analyses predicted the variant to be highly pathogenic (CADD score 29; AlphaMissense score 0.978; PhyloP 8.87; DynaMut ΔΔG = -0.765 kcal·mol-1 and ΔΔSVib = -0.234 kcal·mol-1·K-1). Structural modeling suggested no gross conformational changes but potential effects local conformation and overall function of the protein. We describe a novel ABCC2 mutation associated with Dubin-Johnson Syndrome. This finding expands the spectrum of ABCC2 variants to evaluate in case of hyperbilirubinemia and highlights the importance of genetic testing in unexplained cases of conjugated hyperbilirubinemia.
When Birth Control Turns Biliary: A Rare Case of Profound Hyperbilirubinemia From Oral Contraceptives.
Oral contraceptives (OCs) are extensively utilized and generally considered safe (reference); nonetheless, infrequent hepatobiliary complications such as cholestasis and hyperbilirubinemia have been documented, particularly among individuals with a genetic predisposition. We present a case involving a 19-year-old female who exhibited significant conjugated hyperbilirubinemia shortly after the commencement of OC therapy. Comprehensive investigations ruled out alternative causes, and the findings from liver biopsy, in conjunction with the clinical context, indicated an estrogen-induced cholestatic injury, likely revealing an underlying Dubin-Johnson syndrome. This case underscores the critical necessity of acknowledging hepatic adverse effects associated with estrogen as well as the influence of genetic susceptibility in drug-related adverse events.
Publicações recentes
When Birth Control Turns Biliary: A Rare Case of Profound Hyperbilirubinemia From Oral Contraceptives.
Genetically confirmed Dubin-Johnson syndrome presenting as long-standing isolated conjugated hyperbilirubinaemia.
ATP-binding Cassette Transporter Defects and Their Roles in Hepatic Diseases.
Expert Consensus on the Diagnosis and Management of Inherited Hyperbilirubinemia (2025).
A novel pathogenic variant for dubin-johnson syndrome in a case of hyperbilirubinemia and metabolic associated fatty liver disease.
📚 EuropePMC360 artigos no totalmostrando 81
When Birth Control Turns Biliary: A Rare Case of Profound Hyperbilirubinemia From Oral Contraceptives.
Journal of investigative medicine high impact case reportsGenetically confirmed Dubin-Johnson syndrome presenting as long-standing isolated conjugated hyperbilirubinaemia.
BMJ case reportsATP-binding Cassette Transporter Defects and Their Roles in Hepatic Diseases.
Journal of clinical and translational hepatologyExpert Consensus on the Diagnosis and Management of Inherited Hyperbilirubinemia (2025).
Journal of clinical and translational hepatologyA novel pathogenic variant for dubin-johnson syndrome in a case of hyperbilirubinemia and metabolic associated fatty liver disease.
Scandinavian journal of gastroenterologyDevelopment of a Physiologically Based Model of Bilirubin Metabolism in Health and Disease and Its Comparison With Real-World Data.
CPT: pharmacometrics & systems pharmacologyPFOS-induced black liver and hepatic aging in mice: A new paradigm in environmental hepatotoxicology.
Environment internationalDubin-Johnson Syndrome: An Eight-Year Retrospective Clinicopathological Review from a North Indian Tertiary Center.
Journal of clinical and experimental hepatologyHow useful are the biochemical tests in guiding the diagnostic workup of infantile cholestasis?
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Associationp.Gly693Arg Homozygote Mutation in Dubin-Johnson Syndrome with Atypical Liver Biopsy due to Reactivation of Hepatitis B Concomitant with Persistent Loss of Kidney Function.
Acta medica Indonesiana[Expert consensus on the diagnosis and therapy of inherited hyperbilirubinemia (version 2025)].
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatologyNext-Generation Sequencing in Diagnosis of Monogenic Cholestatic Liver Disorders: A Single-Center Experience.
Molecular syndromologyA recurrent ABCC2 c.2439 + 5G > A variant disturbs mRNA splicing and causes Dubin-Johnson syndrome.
BMC medical genomics[Clinical and molecular genetic analysis of nine patients with neonatal Dubin-Johnson syndrome].
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatologyAn Incidental Finding of an Indigo-Blue Liver in a Patient With Dubin-Johnson Syndrome Confirmed via Genetic Testing.
CureusABCC2 p.R393W variant contributes to Dubin-Johnson syndrome by targeting MRP2 to proteasome degradation.
eGastroenterologyPatterns and unique features of infantile cholestasis among Arabs.
Frontiers in pediatricsCase Report: A case of Dubin-Johnson syndrome in a newborn.
Frontiers in pediatricsStructural basis for the transport and regulation mechanism of the Multidrug resistance-associated protein 2.
bioRxiv : the preprint server for biologyStructural basis for the modulation of MRP2 activity by phosphorylation and drugs.
Nature communicationsDiagnostic algorithm for neonatal intrahepatic cholestasis integrating single-gene testing and next-generation sequencing in East Asia.
Journal of gastroenterology and hepatologyTransport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.
Nature communicationsClinical characteristics and follow-up of a newborn with Dubin-Johnson Syndrome: A clinical case report.
MedicineExcessive vincristine exposure in a child being treated for acute lymphoblastic leukaemia with underlying Dubin-Johnson syndrome: a case report.
Cancer chemotherapy and pharmacologyUrinary coproporphyrins as a diagnostic biomarker of Dubin-Johnson syndrome in neonates: A diagnostic pathway is proposed.
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology AssociationHyperbilirubinemia in a Patient With Sepsis: A Diagnostic Challenge.
ACG case reports journalDubin-Johnson Syndrome: A Case Report.
CureusDifferentiating Neonatal Dubin Johnson Syndrome from Biliary Atresia: Start Simply.
Journal of clinical and translational hepatologyGenotype-Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin-Johnson Syndrome: A Case Report.
International journal of molecular sciencesNeonatal Dubin-Johnson Syndrome and its Differentiation from Biliary Atresia.
Journal of clinical and translational hepatologyConcurrence of novel mutations causing Gilbert's and Dubin-Johnson syndrome with poor clinical outcomes in a Han Chinese family.
Journal of human genetics[The phenotypes and genotypes of four patients with Dubin-Johnson syndrome].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsRotor Syndrome Presenting as Dubin-Johnson Syndrome.
Case reports in gastroenterologyCase Report: Three novel pathogenic ABCC2 mutations identified in two patients with Dubin-Johnson syndrome.
Frontiers in genetics[Genetic analysis of a case with Dubin-Johnson syndrome due to two novel variants of ABCC2 gene].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsClinical features and genetic variations of severe neonatal hyperbilirubinemia: Five case reports.
World journal of clinical casesBenign inheritable disorders of bilirubin metabolism manifested by conjugated hyperbilirubinemia-A narrative review.
United European gastroenterology journalCase Report: Dubin-Johnson Syndrome Presenting With Infantile Cholestasis: An Overlooked Diagnosis in an Extended Family.
Frontiers in pediatricsIn silico screening and analysis of single-nucleotide polymorphic variants of the ABCC2 gene affecting Dubin-Johnson syndrome.
Arab journal of gastroenterology : the official publication of the Pan-Arab Association of GastroenterologyA case of true vocal fold jaundice.
American journal of otolaryngologyReal-life Progression of the Use of a Genetic Panel in to Diagnose Neonatal Cholestasis.
JPGN reportsClinical characteristics and liver profiles of Dubin-Johnson syndrome in neonates: Multicenter retrospective study.
Archives de pediatrie : organe officiel de la Societe francaise de pediatrieClinical, Biochemical, and Molecular Characterization of Neonatal-Onset Dubin-Johnson Syndrome in a Large Case Series From the Arabs.
Frontiers in pediatrics[Clinical and pathological features of Dubin-Johnson syndrome].
Zhonghua bing li xue za zhi = Chinese journal of pathologyLiterature review and report of three cases of Dubin-Johnson syndrome related to ABCC2 gene mutations in children.
American journal of translational researchNeonatal Dubin-Johnson syndrome: biochemical parameters, characteristics, and genetic variants study.
Pediatric researchCharacterization of a novel ABCC2 mutation in infantile Dubin Johnson syndrome.
Clinica chimica acta; international journal of clinical chemistryDubin-Johnson syndrome as a laparoscopic finding.
Revista espanola de enfermedades digestivasClinical characteristics and ABCC2 genotype in Dubin-Johnson syndrome: A case report and review of the literature.
World journal of clinical casesDubin-Johnson Syndrome as Differential Diagnosis for Neonatal Cholestasis.
Journal of pediatric gastroenterology and nutritionA Case of Dubin-Johnson Syndrome Presenting as Neonatal Cholestasis With Paucity of Interlobular Bile Ducts.
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyA novel homozygous frameshift variant in the ABCC2-gene in Dubin-Johnson syndrome may predispose to chronic liver disease.
Indian journal of gastroenterology : official journal of the Indian Society of GastroenterologyDubin-Johnson syndrome coexisting with glucose-6-phosphate dehydrogenase deficiency presenting after acute viral hepatitis.
JPMA. The Journal of the Pakistan Medical AssociationMutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome.
BMC pediatricsA recurrent ABCC2 p.G693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China.
Orphanet journal of rare diseasesDubin-Johnson Syndrome Presenting During Cardiac Transplantation Evaluation.
CureusLaparoscopic cholecystectomy for cholecystolithiasis with Dubin-Johnson syndrome.
JGH open : an open access journal of gastroenterology and hepatologyNext generation sequencing reveals co-existence of hereditary spherocytosis and Dubin-Johnson syndrome in a Chinese gril: A case report.
World journal of clinical casesGenetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders.
Liver international : official journal of the International Association for the Study of the LiverAdult Coats' Disease, Dubin-Johnson Syndrome, and the Search for Targeted Therapies.
Ophthalmic surgery, lasers & imaging retinaA Case of Dubin-Johnson Syndrome in Pregnancy.
Cureus[Diagnosis of a patient with Dubin-Johnson syndrome by using next generation sequencing].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics[Clinical features and ABCC2 genotypic analysis of an infant with Dubin-Johnson syndrome].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics[Clinical and pathological features of inherited metabolic liver disease in adults].
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatologyDubin-Johnson syndrome in Tunisia: Spectrum of a rare disease.
Presse medicale (Paris, France : 1983)Mutation analysis of the ABCC2 gene in Chinese patients with Dubin-Johnson syndrome.
Experimental and therapeutic medicineNovel compound heterozygous ABCC2 variants in patients with Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy.
Clinical geneticsVariants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand.
Journal of pediatric geneticsClinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan.
The Journal of pediatricsHepatobiliary and Pancreatic: A black liver of Dubin-Johnson syndrome.
Journal of gastroenterology and hepatologyConjugated hyperbilirubinemia after surgery. A diagnosis of Dubin-Johnson syndrome confirmed by genetic testing.
Revista espanola de enfermedades digestivasDubin-Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report.
BMC research notesIdentification of a compound heterozygous mutation of ABCC2 in a patient with hyperbilirubinemia.
Molecular medicine reportsA Time-Dependent Model Describes Methotrexate Elimination and Supports Dynamic Modification of MRP2/ABCC2 Activity.
Therapeutic drug monitoringHistopathologic Findings in Autopsies with Emphasis on Interesting and Incidental Findings-A Pathologist's Perspective.
Journal of clinical and diagnostic research : JCDRIMAGES IN CLINICAL MEDICINE. Dubin-Johnson Syndrome.
The New England journal of medicineMolecular Genetic Dissection and Neonatal/Infantile Intrahepatic Cholestasis Using Targeted Next-Generation Sequencing.
The Journal of pediatricsInherited disorders of bilirubin clearance.
Pediatric researchCoronary Artery Disease in Patients With Disorders of Bilirubin Excretion.
American journal of therapeuticsGenetic and biochemical study of dual hereditary jaundice: Dubin-Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2.
European journal of human genetics : EJHGTreatment for tuberculosis in a patient with Dubin-Johnson syndrome.
BMJ case reportsAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Genetically confirmed Dubin-Johnson syndrome presenting as long-standing isolated conjugated hyperbilirubinaemia.
- ATP-binding Cassette Transporter Defects and Their Roles in Hepatic Diseases.
- Expert Consensus on the Diagnosis and Management of Inherited Hyperbilirubinemia (2025).
- A novel pathogenic variant for dubin-johnson syndrome in a case of hyperbilirubinemia and metabolic associated fatty liver disease.
- When Birth Control Turns Biliary: A Rare Case of Profound Hyperbilirubinemia From Oral Contraceptives.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:234(Orphanet)
- OMIM OMIM:237500(OMIM)
- MONDO:0009380(MONDO)
- GARD:2793(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Artigo Wikipedia(Wikipedia)
- Q1263039(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar