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Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Alagille’s syndrome is an autosomal dominant disorder in which there is paucity of the intrahepatic bile ducts. The resultant chronic cholestasis causes jaundice, pruritis and hypercholesterolemia. Dysmorphic faces, cardiac anomalies, vertebral anomalies, failure to thrive and developmental delay are features of the syndrome. Budd–Chiari’s syndrome is a rare condition in which there is obstruction of the hepatic veins. Gilbert’s syndrome is a usually harmless condition in which reduced levels of a particular enzyme (uridine-diphosphate glucuronosyltransferase) in the liver results in slightly raised serum bilirubin levels. Criggler–Najjar’s syndrome is a rare disorder in which a defective enzyme results in defective breakdown of bile, causing its levels to rise.
UGT1A1 Polymorphisms and Mutations Affect Anticancer Drug Therapy
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Tristan M. Sissung, Roberto Barbier, Lisa M. Cordes, William D. Figg
Variants in the UGT1A1 gene are also responsible for the more common and mild hyperbilirubinemia observed in the 3–7% of the United States population with Gilbert’s syndrome [42]. Gilbert’s syndrome is associated with homozygous (TA)7TAA alleles (versus (TA)6TAA in wild-type individuals), referred to as UGT1A1*28 as previously described [6, 7, 12, 43, 50]. The UGT1A1 promoter can also consist of (TA)5TAA and (TA)8TAA alleles, although these alleles are poorly studied. Such variation leads to up to a 70% reduction in UGT1A1 activity [44, 49] resulting in an elevated level of unconjugated bilirubin in the bloodstream. Hyperbilirubinemia in Gilbert’s syndrome is typically benign, with serum bilirubin concentrations rarely exceeding 5 mg/dL and typically fluctuating between 1.3 and 3 mg/dL [39]. There are usually no serious consequences associated with this disease; mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. Gilbert’s syndrome is thus considered an entirely benign and clinically inconsequential entity requiring neither treatment nor long-term medical attention, although mild hyperbilirubinemia is sometimes mistaken for a sign of occult, chronic, or progressive liver disease [50]. Gilbert’s syndrome is generally considered to be an autosomal recessive disorder. However, some cases of heterozygosity and compound heterozygosity have been reported in patients with Gilbert syndrome, predominantly among the Asian population [33].
SBA Answers and Explanations
Published in Vivian A. Elwell, Jonathan M. Fishman, Rajat Chowdhury, SBAs for the MRCS Part A, 2018
Vivian A. Elwell, Jonathan M. Fishman, Rajat Chowdhury
Gilbert syndrome is an autosomal recessive inherited metabolic disorder (although occasionally inherited in an autosomal dominant fashion depending on the type of mutation), causing increased levels of unconjugated bilirubin in the blood. It is a common hereditary cause of hyperbilirubinaemia. There is decreased activity of the enzyme glucuronyltransferase, which conjugates bilirubin in the liver. Bilirubin is excreted from the body only in the conjugated form. Typical presentation is painless jaundice during an intercurrent illness.
Strategies to overcome the diagnostic challenges of autoimmune hemolytic anemias
Published in Expert Review of Hematology, 2023
Wilma Barcellini, Bruno Fattizzo
All the described hemolytic markers have several coexisting confounding conditions that may puzzle their interpretation [40]. Underdiagnosed blood loss, vitamin/iron deficiency, renal/liver disease, and erythropoietin insufficiency may contribute to anemia. LDH is increased in several diseases that involve cellular necrosis or increased tissue turnover (myocardial infarction, heart failure, hepatitis, extreme muscular effort, and solid and hematologic tumors). Unconjugated bilirubin is typically increased in Gilbert’s syndrome, and mixed hyperbilirubinemia in liver disease. Haptoglobin, may be falsely normal/raised in inflammatory diseases, cigarette smokers, and nephritic syndrome possibly masking an underlying hemolysis; conversely, it may be reduced for liver disease, malnutrition, and congenital hypo-haptoglobinemia, without a hemolytic disease. Reticulocytes, that are not ‘truly’ hemolytic markers, may be increased in other causes of anemia requiring bone marrow compensation, such as hemorrhage, pregnancy/delivery and acclimatation. At variance a coexisting underdiagnosed bone marrow disease (myelodysplasia, aplasia, leukemia, tumors) may impair an adequate reticulocyte compensation.
The brain heme oxygenase/biliverdin reductase system as a target in drug research and development
Published in Expert Opinion on Therapeutic Targets, 2022
With regard to BR, whose formation requires BVR, its neuroprotective function relies on several mechanisms, whose main ones are summarized in Figure 2. An enhanced systemic antioxidant response was described in subjects with Gilbert’s syndrome, a benign genetic disorder characterized by free (unconjugated) hyperbilirubinemia (< 85 µM) secondary to both increased HO-1 and BVR expression and reduced UGT1A1 activity (UGT1A1*28 polymorphism) [7,82]. Retrospective and protective studies have shown that people with Gilbert’s syndrome have a reduced risk of cardiovascular diseases (e.g. coronary heart disease, myocardial infarction) and other inflammatory disorders [82,83]. However, no significant data currently support a similar trend toward neurodegenerative and other brain disorders. A possible reason for such a lack of evidence depends on the fact that brain tissue is very sensitive to the neurotoxic effects of BR (Figure 2), which can synergize with those related to neurodegenerative processes.
Neonatal hyperbilirubinaemia and type I diabetes: an unsolved enigma
Published in Paediatrics and International Child Health, 2020
Jogender Kumar, Jaivinder Yadav
In spite of intensive research on the association between type 1 diabetes mellitus (T1DM) and neonatal hyperbili-rubinaemia, the mystery remains unsolved. A recently article by Liao et al. in Paediatrics and International Child Health estimated that neonates with hyperbilirubinaemia might have a 66% higher risk of developing T1DM in childhood [1]. Around 60% of term and 80% of preterm neonates have physiological jaundice. Bilirubin is known for its anti-oxidant and anti-inflammatory properties and is considered to have a protective effect against hypertension, ischaemic heart disease, type II diabetes (T2D), metabolic syndrome and obesity [2]. Bilirubin is protective against complications of T2D and is being explored as a potential biomarker and therapeutic target for type I diabetic nephropathy [3,4]. Individuals with Gilbert syndrome are protected against diabetes and its complications by virtue of elevated bilirubin levels [5]. Bilirubin production peaks at the time of maximum oxidative stress (probably a protective agent) in the newborn [6,7]. The results of Liao et al.’s study raise serious concerns over the existence of this natural anti-oxidant and need to be explained.