RARE DISEASE
Dubin-Johnson syndrome
Dubin-Johnson syndrome
Dubin-Johnson syndrome
Synonyms: Dubin-Sprinz disease, Hyperbilirubinemia type 2, Sprinz-Nelson syndrome
Synonyms: Dubin-Sprinz disease, Hyperbilirubinemia type 2, Sprinz-Nelson syndrome
Synonyms: Dubin-Sprinz disease, Hyperbilirubinemia type 2, Sprinz-Nelson syndrome
Drug discovery
0
drugs
With orphan designations
Overview
Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder caused by mutations in the ABCC2 gene, impairing hepatic excretion of conjugated bilirubin. It presents with chronic, predominantly conjugated hyperbilirubinemia and recurrent jaundice, often triggered by stressors like infection or pregnancy. Diagnosis is confirmed by elevated urinary coproporphyrin I (>80% of total) and genetic testing. Liver biopsy reveals characteristic melanin-like pigment deposition. The disease is benign, with normal liver function and no progression to fibrosis [1][2][7][10][12].
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism
Research Papers
51 drug discovery papers about Dubin-Johnson syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
51 drug discovery papers about Dubin-Johnson syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
2026-04-09 | Dubin-Johnson and Rotor Syndromes: A Review and Update of Pathophysiological Mechanisms
Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders that result in chronic, predominantly conjugated hyperbilirubinemia without cholestasis or hepatocellular injury. Although both conditions are benign and non-progressive, they reflect distinct molecular defects in hepatocellular transport pathways. DJS arises from mutations in the ABCC2 gene encoding the canalicular transporter multidrug resistance–associated protein 2, leading to impaired biliary excretion of conjugated bilirubin and organic anions. In contrast, RS results from combined deficiencies of the sinusoidal transporters OATP1B1 and OATP1B3, encoded by SLCO1B1 and SLCO1B3 genes, respectively, which mediate hepatic reuptake of conjugated bilirubin from the sinusoidal blood. These defects explain the characteristic biochemical and clinical distinctions between the syndromes, including the black hepatic pigmentation and markedly elevated urinary coproporphyrin I fraction in DJS, and the absence of pigmentation with moderate coproporphyrin I predominance in RS. Recent studies have expanded the understanding of how these transporters influence not only bilirubin handling but also the hepatic disposition of various drugs and endogenous metabolites. Recognition of DJS and RS is essential to prevent misdiagnosis of cholestatic or hepatocellular disease, avoid unnecessary investigations, and anticipate altered pharmacokinetics in affected individuals. This review synthesizes current evidence from molecular, biochemical, and clinical studies to highlight how these syndromes illuminate broader principles of hepatic transporter physiology and its relevance to inherited and acquired disorders of bilirubin metabolism.
2026-01-30 | Autoimmune encephalopathy in a patient with coexisting rare genetic syndromes: PMM2-CDG and Dubin–Johnson
Introduction: MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare mitochondrial disorder with progressive neurological decline, seizures, and cognitive impairment. When encephalopathy occurs in patients with overlapping rare syndromes, diagnostic clarification becomes particularly complex. We report a case of encephalopathy in a patient with MELAS, also carrying PMM2-CDG and Dubin-Johnson syndrome, currently under investigation for a possible autoimmune etiology. Objective and methods: To describe the clinical course of autoimmune encephalopathy in a 41-year-old woman with rare metabolic conditions identified by whole exome and mitochondrial DNA sequencing. No interventions were performed; data were collected exclusively from clinical records during hospitalization at the Hospital de Doenças Tropicais. Results: The patient presented progressive neurological decline since age 27, starting with seizures and followed by outpatient care. In 2023, genetic testing revealed mutations consistent with PMM2-CDG and Dubin-Johnson syndrome. Clinical criteria for MELAS were also met. Two weeks before admission, she developed mental confusion and hyporesponsiveness. Central nervous system vasculitis was initially suspected. Cerebrospinal fluid (CSF) analysis showed isolated oligoclonal bands, and the autoimmune panel was indeterminate for anti-beta-2 glycoprotein I. Pulse therapy with methylprednisolone was initiated, followed by prednisone and azathioprine. A working diagnosis of autoimmune encephalopathy is under investigation. Rituximab is under consideration. Conclusion: This rare case highlights the diagnostic complexity posed by overlapping genetic and autoimmune processes. The inflammatory CSF profile and partial response to immunosuppression support an autoimmune component. Genetic screening was key in guiding management.
2025-06-18 | [Clinical and molecular genetic analysis of nine patients with neonatal Dubin-Johnson syndrome].
Objective: Dubin-Johnson syndrome (DJS) is a hereditary liver disease caused by biallelic pathogenic variants in the ABCC2 gene. As a rare disease, the ABCC2 genotype and clinical phenotype characteristics of DJS patients still need to be summarized in depth. Methods: Nine cases diagnosed with DJS and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University were collected as the study subjects. Clinical and laboratory data, general information, symptoms, signs, pathological changes, treatment, and prognostic conditions were systematically analyzed. Targeted high-throughput sequencing was used to detect hereditary diseases. The positive results for the family lineage were verified by Sanger sequencing. The pathogenicity of the novel ABCC2 variants was evaluated according to the American College of Medical Genetics and Genomics guidelines and standards. One-way analysis of variance or Kruskal-Wallis test was used to compare the statistical differences between multiple groups of data. Results: Among the nine DJS cases, seven and two were males, and females. All of them had the initial symptom of jaundice (100%), with a median age of onset of 5 (2,15) days. During the course of the disease, seven (7/9) and two (2/9) cases had hepatomegaly and splenomegaly. All of the patients exhibited direct hyperbilirubinemia, concurrently with elevated total bile acids (TBA) and γ-glutamyl transferase (GGT). Serum transaminases (4/9) and alkaline phosphatase levels (3/9) were elevated in some patients. A total of twelve types of ABCC2 variants were detected in nine cases, of which c.2362_2363del (p.Leu788ValfsTer13), c.364C>T (p.Gln122Ter), c.338T>C (p.Leu113Pro) and c.419T>A (p.Ile140Lys) were novel pathogenic/likely pathogenic variants. Jaundice disappeared and alleviated in five cases (5/9) and four cases (4/9), while hepatomegaly improved in five cases (5/9) at the last follow-up at 7.79 (7.0,15.25) months following treatment with drugs such as liver protectives, choleretics, and jaundice-reducing agents. Among them, three cases (3/9) had a normal restored liver size. All patients had varying degrees of improvement in bilirubin, TBA, GGT, and ALP levels. Conclusions: The onset of high GGT cholestatic jaundice is the main clinical manifestation in patients with neonatal DJS. The genetic analysis results showed four novel types of variants, which expanded the ABCC2 gene variation spectrum, providing novel molecular markers for confirming a diagnosis of DJS. The patient's clinical manifestations and laboratory abnormalities improved or disappeared after internal medicine treatment, suggesting that DJS may be a type of genetic disease with a favorable long-term prognosis.
2025-05-01 | Dubin-Johnson Syndrome and Familial Hypercholanemia Type 2 in Infant Patient - Impact of Two Genes on Liver Cholestasis: Case Report and Literature Review
Background: Dubin-Johnson syndrome (DJS) and familial hypercholanemia (FHC) are rare hereditary cholestatic liver diseases affecting bilirubin and bile acid metabolism, respectively.DJS is characterized by chronic conjugated hyperbilirubinemia without significant liver dysfunction, whereas FHC leads to elevated serum bile acids and potential malabsorption of fat-soluble vitamins.While both conditions have been individually reported, their coexistence in a single patient is extremely rare.This case report describes a pediatric patient diagnosed with both conditions, highlighting the unique genetic findings and clinical presentation.It contributes to the understanding of overlapping cholestatic disorders and emphasizes the role of genetic testing in early diagnosis and management. Case Summary:We report the case of a 13-month-old Chinese male who presented with persistent jaundice since birth, scleral icterus, and clay-colored stools.Liver function tests showed direct hyperbilirubinemia with mild transaminases and preserved synthetic liver function.Imaging studies, including hepatobiliary scintigraphy, ruled out biliary atresia.A comprehensive genetic panel identified two heterozygous variants in the ABCC2 gene, suggestive of DJS, and a heterozygous pathogenic variant in the SLC10A1 gene, associated with FHC2.Our patient remained asymptomatic, with only transitory peaks of mildly elevated transaminases.Treatment with ursodeoxycholic acid and fat-soluble vitamin supplementation led to improvement. Conclusion:This case highlights the clinical implications of coexisting DJS and FHC2.It underscores the importance of genetic testing in pediatric cholestatic liver diseases for accurate diagnosis and tailored management.The coexistence of DJS and FHC2 suggests that multiple genetic defects may contribute to disease severity, necessitating long-term follow-up and monitoring for potential complications. Core TipThis case report describes a rare paediatric patient with coexisting Dubin-Johnson syndrome (DJS) and familial hypercholanemia type 2 (FHC2), both contributing to neonatal cholestatic liver disease.Genetic testing revealed two heterozygous ABCC2 variants linked to DJS and a heterozygous pathogenic SLC10A1 variant associated with FHC2.The patient remained asymptomatic with transitory peaks of mild liver enzyme elevation, improving with ursodeoxycholic acid and vitamin supplementation.This case highlights the significance of genetic testing in diagnosing rare cholestatic disorders and the potential impact of dual genetic mutations on disease presentation and management.
2024-08-05 | Case Report: A case of Dubin-Johnson syndrome in a newborn.
Dubin-Johnson Syndrome (DJS) is a rare autosomal recessive genetic disorder, with most cases presenting in adolescence, but rare in newborns. To investigate the clinical characteristics and treatment outcomes of DJS in a newborn. We present the clinical features of a newborn diagnosed with DJS through molecular genetic testing. The patient was a male newborn who developed jaundice and scleral icterus on the 6th day of life. Both direct and indirect bilirubin levels were elevated. After treatment with phototherapy, indirect bilirubin levels decreased, but direct bilirubin remained unchanged, and the stool color gradually lightened. At 56 days of age, the patient underwent laparoscopic cholecystostomy, which revealed viscous bile plugs in the bile ducts. Following the surgery, the patient received oral ursodeoxycholic acid, compound glycyrrhizin, and methylprednisolone. Follow-up until one year post-surgery showed a gradual reduction in direct bilirubin levels to the normal range. Molecular genetic testing revealed three heterozygous mutations in the ABCC2 gene on chromosome 10, with one pathogenic variant inherited from the father and two from the mother, confirming the diagnosis of DJS. DJS is a benign condition with a favorable prognosis. In newborns, it should be differentiated from other causes of cholestasis, and compared to cholestasis, jaundice in newborns with DJS responds more slowly to treatment.
2026-04-09 | Dubin-Johnson and Rotor Syndromes: A Review and Update of Pathophysiological Mechanisms
Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders that result in chronic, predominantly conjugated hyperbilirubinemia without cholestasis or hepatocellular injury. Although both conditions are benign and non-progressive, they reflect distinct molecular defects in hepatocellular transport pathways. DJS arises from mutations in the ABCC2 gene encoding the canalicular transporter multidrug resistance–associated protein 2, leading to impaired biliary excretion of conjugated bilirubin and organic anions. In contrast, RS results from combined deficiencies of the sinusoidal transporters OATP1B1 and OATP1B3, encoded by SLCO1B1 and SLCO1B3 genes, respectively, which mediate hepatic reuptake of conjugated bilirubin from the sinusoidal blood. These defects explain the characteristic biochemical and clinical distinctions between the syndromes, including the black hepatic pigmentation and markedly elevated urinary coproporphyrin I fraction in DJS, and the absence of pigmentation with moderate coproporphyrin I predominance in RS. Recent studies have expanded the understanding of how these transporters influence not only bilirubin handling but also the hepatic disposition of various drugs and endogenous metabolites. Recognition of DJS and RS is essential to prevent misdiagnosis of cholestatic or hepatocellular disease, avoid unnecessary investigations, and anticipate altered pharmacokinetics in affected individuals. This review synthesizes current evidence from molecular, biochemical, and clinical studies to highlight how these syndromes illuminate broader principles of hepatic transporter physiology and its relevance to inherited and acquired disorders of bilirubin metabolism.
2026-01-30 | Autoimmune encephalopathy in a patient with coexisting rare genetic syndromes: PMM2-CDG and Dubin–Johnson
Introduction: MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare mitochondrial disorder with progressive neurological decline, seizures, and cognitive impairment. When encephalopathy occurs in patients with overlapping rare syndromes, diagnostic clarification becomes particularly complex. We report a case of encephalopathy in a patient with MELAS, also carrying PMM2-CDG and Dubin-Johnson syndrome, currently under investigation for a possible autoimmune etiology. Objective and methods: To describe the clinical course of autoimmune encephalopathy in a 41-year-old woman with rare metabolic conditions identified by whole exome and mitochondrial DNA sequencing. No interventions were performed; data were collected exclusively from clinical records during hospitalization at the Hospital de Doenças Tropicais. Results: The patient presented progressive neurological decline since age 27, starting with seizures and followed by outpatient care. In 2023, genetic testing revealed mutations consistent with PMM2-CDG and Dubin-Johnson syndrome. Clinical criteria for MELAS were also met. Two weeks before admission, she developed mental confusion and hyporesponsiveness. Central nervous system vasculitis was initially suspected. Cerebrospinal fluid (CSF) analysis showed isolated oligoclonal bands, and the autoimmune panel was indeterminate for anti-beta-2 glycoprotein I. Pulse therapy with methylprednisolone was initiated, followed by prednisone and azathioprine. A working diagnosis of autoimmune encephalopathy is under investigation. Rituximab is under consideration. Conclusion: This rare case highlights the diagnostic complexity posed by overlapping genetic and autoimmune processes. The inflammatory CSF profile and partial response to immunosuppression support an autoimmune component. Genetic screening was key in guiding management.
2025-06-18 | [Clinical and molecular genetic analysis of nine patients with neonatal Dubin-Johnson syndrome].
Objective: Dubin-Johnson syndrome (DJS) is a hereditary liver disease caused by biallelic pathogenic variants in the ABCC2 gene. As a rare disease, the ABCC2 genotype and clinical phenotype characteristics of DJS patients still need to be summarized in depth. Methods: Nine cases diagnosed with DJS and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University were collected as the study subjects. Clinical and laboratory data, general information, symptoms, signs, pathological changes, treatment, and prognostic conditions were systematically analyzed. Targeted high-throughput sequencing was used to detect hereditary diseases. The positive results for the family lineage were verified by Sanger sequencing. The pathogenicity of the novel ABCC2 variants was evaluated according to the American College of Medical Genetics and Genomics guidelines and standards. One-way analysis of variance or Kruskal-Wallis test was used to compare the statistical differences between multiple groups of data. Results: Among the nine DJS cases, seven and two were males, and females. All of them had the initial symptom of jaundice (100%), with a median age of onset of 5 (2,15) days. During the course of the disease, seven (7/9) and two (2/9) cases had hepatomegaly and splenomegaly. All of the patients exhibited direct hyperbilirubinemia, concurrently with elevated total bile acids (TBA) and γ-glutamyl transferase (GGT). Serum transaminases (4/9) and alkaline phosphatase levels (3/9) were elevated in some patients. A total of twelve types of ABCC2 variants were detected in nine cases, of which c.2362_2363del (p.Leu788ValfsTer13), c.364C>T (p.Gln122Ter), c.338T>C (p.Leu113Pro) and c.419T>A (p.Ile140Lys) were novel pathogenic/likely pathogenic variants. Jaundice disappeared and alleviated in five cases (5/9) and four cases (4/9), while hepatomegaly improved in five cases (5/9) at the last follow-up at 7.79 (7.0,15.25) months following treatment with drugs such as liver protectives, choleretics, and jaundice-reducing agents. Among them, three cases (3/9) had a normal restored liver size. All patients had varying degrees of improvement in bilirubin, TBA, GGT, and ALP levels. Conclusions: The onset of high GGT cholestatic jaundice is the main clinical manifestation in patients with neonatal DJS. The genetic analysis results showed four novel types of variants, which expanded the ABCC2 gene variation spectrum, providing novel molecular markers for confirming a diagnosis of DJS. The patient's clinical manifestations and laboratory abnormalities improved or disappeared after internal medicine treatment, suggesting that DJS may be a type of genetic disease with a favorable long-term prognosis.
2025-05-01 | Dubin-Johnson Syndrome and Familial Hypercholanemia Type 2 in Infant Patient - Impact of Two Genes on Liver Cholestasis: Case Report and Literature Review
Background: Dubin-Johnson syndrome (DJS) and familial hypercholanemia (FHC) are rare hereditary cholestatic liver diseases affecting bilirubin and bile acid metabolism, respectively.DJS is characterized by chronic conjugated hyperbilirubinemia without significant liver dysfunction, whereas FHC leads to elevated serum bile acids and potential malabsorption of fat-soluble vitamins.While both conditions have been individually reported, their coexistence in a single patient is extremely rare.This case report describes a pediatric patient diagnosed with both conditions, highlighting the unique genetic findings and clinical presentation.It contributes to the understanding of overlapping cholestatic disorders and emphasizes the role of genetic testing in early diagnosis and management. Case Summary:We report the case of a 13-month-old Chinese male who presented with persistent jaundice since birth, scleral icterus, and clay-colored stools.Liver function tests showed direct hyperbilirubinemia with mild transaminases and preserved synthetic liver function.Imaging studies, including hepatobiliary scintigraphy, ruled out biliary atresia.A comprehensive genetic panel identified two heterozygous variants in the ABCC2 gene, suggestive of DJS, and a heterozygous pathogenic variant in the SLC10A1 gene, associated with FHC2.Our patient remained asymptomatic, with only transitory peaks of mildly elevated transaminases.Treatment with ursodeoxycholic acid and fat-soluble vitamin supplementation led to improvement. Conclusion:This case highlights the clinical implications of coexisting DJS and FHC2.It underscores the importance of genetic testing in pediatric cholestatic liver diseases for accurate diagnosis and tailored management.The coexistence of DJS and FHC2 suggests that multiple genetic defects may contribute to disease severity, necessitating long-term follow-up and monitoring for potential complications. Core TipThis case report describes a rare paediatric patient with coexisting Dubin-Johnson syndrome (DJS) and familial hypercholanemia type 2 (FHC2), both contributing to neonatal cholestatic liver disease.Genetic testing revealed two heterozygous ABCC2 variants linked to DJS and a heterozygous pathogenic SLC10A1 variant associated with FHC2.The patient remained asymptomatic with transitory peaks of mild liver enzyme elevation, improving with ursodeoxycholic acid and vitamin supplementation.This case highlights the significance of genetic testing in diagnosing rare cholestatic disorders and the potential impact of dual genetic mutations on disease presentation and management.
2024-08-05 | Case Report: A case of Dubin-Johnson syndrome in a newborn.
Dubin-Johnson Syndrome (DJS) is a rare autosomal recessive genetic disorder, with most cases presenting in adolescence, but rare in newborns. To investigate the clinical characteristics and treatment outcomes of DJS in a newborn. We present the clinical features of a newborn diagnosed with DJS through molecular genetic testing. The patient was a male newborn who developed jaundice and scleral icterus on the 6th day of life. Both direct and indirect bilirubin levels were elevated. After treatment with phototherapy, indirect bilirubin levels decreased, but direct bilirubin remained unchanged, and the stool color gradually lightened. At 56 days of age, the patient underwent laparoscopic cholecystostomy, which revealed viscous bile plugs in the bile ducts. Following the surgery, the patient received oral ursodeoxycholic acid, compound glycyrrhizin, and methylprednisolone. Follow-up until one year post-surgery showed a gradual reduction in direct bilirubin levels to the normal range. Molecular genetic testing revealed three heterozygous mutations in the ABCC2 gene on chromosome 10, with one pathogenic variant inherited from the father and two from the mother, confirming the diagnosis of DJS. DJS is a benign condition with a favorable prognosis. In newborns, it should be differentiated from other causes of cholestasis, and compared to cholestasis, jaundice in newborns with DJS responds more slowly to treatment.
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