ABSTRACT
Coats' disease is nonhereditary retinal vascular disorder characterized by telangiectatic retinal vessels with prominent aneurysmal changes and exudation. A conclusive etiology has not yet been determined. In this retrospective case report and literature review, a 64-year-old male with Dubin-Johnson syndrome presented with unilateral retinal vascular changes and exudation consistent with a diagnosis of adult Coats' disease. The authors conclude that patients with Dubin-Johnson syndrome carry mutations in a multidrug resistance associated protein (MRP). MRPs are also expressed in the retina, retinal pigment epithelium, and vascular endothelium, where they export toxins and metabolites, and may serve as a therapeutic target. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:318-321.].
Subject(s)
Jaundice, Chronic Idiopathic/diagnosis , Laser Therapy/methods , Retinal Pigment Epithelium/pathology , Retinal Telangiectasis/diagnosis , Retinal Vessels/diagnostic imaging , Fluorescein Angiography , Fundus Oculi , Humans , Jaundice, Chronic Idiopathic/therapy , Male , Middle Aged , Retinal Telangiectasis/surgery , Retinal Vessels/surgery , Tomography, Optical CoherenceABSTRACT
Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.
Subject(s)
Genetic Therapy , Jaundice/genetics , Jaundice/therapy , Animals , Crigler-Najjar Syndrome , Gene Transfer Techniques , Genetic Vectors/genetics , Gilbert Disease , Humans , Hyperbilirubinemia, Hereditary/diagnosis , Hyperbilirubinemia, Hereditary/genetics , Hyperbilirubinemia, Hereditary/therapy , Jaundice, Chronic Idiopathic/diagnosis , Jaundice, Chronic Idiopathic/genetics , Jaundice, Chronic Idiopathic/therapy , Liver/metabolism , Liver/pathologySubject(s)
Liver Diseases/genetics , Metabolism, Inborn Errors/genetics , Molecular Biology , Animals , Bilirubin/metabolism , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/genetics , Cholestasis, Intrahepatic/therapy , Cystic Fibrosis/complications , Cystic Fibrosis/genetics , Cystic Fibrosis/therapy , Disease Models, Animal , Genetic Therapy , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/genetics , Hepatolenticular Degeneration/therapy , Humans , Jaundice, Chronic Idiopathic/complications , Jaundice, Chronic Idiopathic/genetics , Jaundice, Chronic Idiopathic/therapy , Liver Diseases/therapy , Metabolism, Inborn Errors/therapy , Tyrosine/blood , alpha 1-Antitrypsin/metabolismSubject(s)
Hyperbilirubinemia, Hereditary , Jaundice, Chronic Idiopathic , Animals , Bilirubin/metabolism , Humans , Hyperbilirubinemia, Hereditary/diagnosis , Hyperbilirubinemia, Hereditary/physiopathology , Hyperbilirubinemia, Hereditary/therapy , Jaundice, Chronic Idiopathic/diagnosis , Jaundice, Chronic Idiopathic/epidemiology , Jaundice, Chronic Idiopathic/physiopathology , Jaundice, Chronic Idiopathic/therapy , Liver/metabolism , Liver/pathologyABSTRACT
Case reports of 4 patients with Rotor syndrome are given, including clinical chemistry values for liver function, BSP-test, histology, as well as sequential scintigraphy results with 131I-BSP. All results were normal, except serum bilirubin, which was increased, conjugated bilirubin making up for the largest part of the increase. The BSP-curve showed elevated 45-minute-values and liver scintigraphy disturbed hepatic uptake and storage of BSP. Therapy with phenobarbital led to a decrease of serum levels of bilirubin and BSP-retention.
