Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The Dubin-Johnson syndrome is often seen in young people and is familial in most cases, originating from an inborn error. The presence of mild and asymptomatic jaundice may be detected in early childhood. The severe form is precipitated by chronic physical exhaustion, alcoholism, infectious diseases, and pregnancy. Abdominal pain in the liver region is the major clinical sign of the disease. Serum bilirubin levels fluctuate from normal values up to 19 mg/dl. The amounts of conjugated bilirubin show variations although glucuronide production is normal. The usual liver tests are also normal or slightly impaired. The abnormality leading to this disorder lies in a primary defect of the hepatic excretory mechanism, since in normal circumstances lipofuscin-type pigments are eliminated from the liver via the bile.
Physiology and Disorders of Human Bilirubin Metabolism
Karel P. M. Heirwegh, Stanley B. Brown in Bilirubin, 1982
Rotor’s syndrome,253 as described in 1948, is a benign, familial, chronic or fluctuating, predominantly conjugated hyperbilirubinemia. For years, it has been considered as a variant of the Dubin-Johnson syndrome, related to an excretory defect, but without pigment deposition in the liver. The most striking argument favoring this relationship was the report of two patients in the same family with Dubin-Johnson syndrome, whereas a third had Rotor’s syndrome.254
The gastrointestinal tract
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
The hyperbilirubinaemias are a heterogeneous group, including the following conditions: Dubin-Johnson syndrome: A variable autosomal dominant that rarely causes significant symptoms.
Unexplained cholestasis in adults and adolescents: diagnostic benefit of genetic examination
Published in Scandinavian Journal of Gastroenterology, 2018
Luise Aamann, Nikolaj Ørntoft, Ida Vogel, Henning Grønbaek, Naja Becher, Hendrik Vilstrup, Peter Ott, Dorte Launholt Lildballe
Mutations in ABCC2 cause the benign autosomal recessive disorder Dubin–Johnson syndrome, which is normally not associated with other signs of cholestasis. However, variants in ABCC2 seem to predispose for cholestatic reactions in some cases. Thus, although not uncontroversial [20,23] ABCC2 mutations have been associated with rare cases of ICP [24,25], neonatal cholestasis [26] and drug interaction involving NSAID and methotrexate [27]. P06 experienced ICP twice, cholestatic symptoms after use of NSAID, and revealed a family history of unexplained cholestatic liver diseases, but as the family was not genetically tested, she was classified as C, ‘Genetics may contribute’. The same was the case for P25 with severe and prolonged cholestatic symptoms after exposure to methotrexate transported by ABCC2 during elimination [28]. P22 presented with congenital hepatic fibrosis in a liver biopsy, this finding was inconsistent with only one missense variant in ABCC2 (c.1483A > G) and therefore classified as C. P22 was later diagnosed with TMEM67 mutations, which explained his phenotype better [29].
Diagnostic criteria and contributors to Gilbert’s syndrome
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Karl-Heinz Wagner, Ryan G. Shiels, Claudia Anna Lang, Nazlisadat Seyed Khoei, Andrew C. Bulmer
Dubin-Johnson syndrome is associated with multidrug resistance-associated protein 2 (MRP2) deficiency, which limits active transport of DBIL into the bile. DBIL therefore refluxes from the liver back into the circulation and causes increased TB and DBIL in the blood. In addition, the patients would likely demonstrate jaundice, produce dark urine, and demonstrate liver histology with course granulation within hepatocytes [68].
Related Knowledge Centers
- Chromosome 10
- Glucuronide
- Porphyrin
- Bilirubin
- Dominance
- Rotor Syndrome
- Multidrug Resistance-Associated Protein 2
- Multiple Drug Resistance
- Autopsy
- Bile Canaliculus