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Trends in Psychiatry and Psychotherapy 2021Gilbert's syndrome (GS) is a benign genetic disorder that is characterized by intermittent mild jaundice in which the liver doesn't process bilirubin properly. The aim...
OBJECTIVE
Gilbert's syndrome (GS) is a benign genetic disorder that is characterized by intermittent mild jaundice in which the liver doesn't process bilirubin properly. The aim of this study was to determine whether GS patients have a different personality structure and if there are associations between properties of temperament and character and total bilirubin levels.
METHODS
A total of 1665 young male individuals aged from 19 to 30 who were admitted for occupational examinations were included in this study. Careful patient history was taken, a detailed physical examination was conducted, and hematologic and biochemical tests and abdominal ultrasonography were performed. The Turkish version of the Temperament and Character Inventory (TCI) was administered to all participants. 81 patients diagnosed with GS and 150 randomly chosen healthy individuals (control group) were investigated with comparison and correlation analyses.
RESULTS
GS patients had higher scores than healthy controls for disorderliness (NS4) (p = 0.018), sentimentality (RD1) (p = 0.042), and fatigability (HA4) (p = 0.03). Moreover, Gilbert syndrome patients scored lower than controls for empathy (C2) (p = 0.041) and transpersonal identification (ST2) (p = 0.044). Bilirubin levels were positively associated with disorderliness (NS4) (r = 0.141, p = 0.032) and fatigability (HA4) (r = 0.14, p = 0.033).
CONCLUSIONS
GS patients may have some different personality characteristics from healthy individuals. This study is an initial exploration of the personality structure of GS patients and the findings should be interpreted with caution. Further prospective studies are needed to identify the relationship between Gilbert disease and personality characteristics.
Topics: Bilirubin; Gilbert Disease; Humans; Male; Personality; Personality Disorders
PubMed: 33844900
DOI: 10.47626/2237-6089-2020-0003 -
United European Gastroenterology Journal Sep 2022Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated... (Review)
Review
Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. Hyperbilirubinemia is an important clinical sign that needs to be investigated under a stepwise evaluation. Inherited non-hemolytic conjugated hyperbilirubinemic conditions include Dubin-Johnson syndrome (caused by mutations affecting ABCC2 gene) and Rotor syndrome (caused by the simultaneous presence of mutations in SLCO1B1 and SLCO1B3 genes). Although classically viewed as benign conditions requiring no treatment, they lately gained an increased interest since recent studies suggested that mutations in the responsible genes leading to hyperbilirubinemia, as well as minor genetic variants, may result in an increased susceptibility to drug toxicity. This article provides a comprehensive review on the pathophysiology of Dubin-Johnson and Rotor syndromes, presenting the current knowledge concerning the molecular details and basis of these conditions.
Topics: Bilirubin; Heme; Humans; Hyperbilirubinemia; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Liver-Specific Organic Anion Transporter 1
PubMed: 35860851
DOI: 10.1002/ueg2.12279 -
European Journal of Haematology Jun 2023Hereditary hemolytic anemias (HHA) comprise a heterogeneous group of disorders resulting from defective red blood cell (RBC) cytoskeleton, RBC enzyme deficiencies, and...
INTRODUCTION
Hereditary hemolytic anemias (HHA) comprise a heterogeneous group of disorders resulting from defective red blood cell (RBC) cytoskeleton, RBC enzyme deficiencies, and hemoglobin (Hb) synthesis disorders such as thalassemia or sideroblastic anemia.
MATERIALS AND METHODS
Our hemolytic anemia diagnostic next-generation sequencing (NGS) panel includes 28 genes encoding RBC cytoskeletal proteins, membrane transporter, RBC enzymes, and certain bilirubin metabolism genes. The panel covers the complete coding region of these genes, splice junctions, and, wherever appropriate, deep intronic or regulatory regions are also included. Four hundred fifty-six patients with unexplained hemolytic anemia were evaluated using our NGS panel between 2015 and 2019.
RESULTS
We identified pathogenic/likely pathogenic variants in 111/456 (24%) patients that were responsible for the disease phenotype (e.g., moderate to severe hemolytic anemia and hyperbilirubinemia). Approximately 40% of the mutations were novel. As expected, 45/456 (10%) patients were homozygous for the promoter polymorphism in the UGT1A1 gene, A(TA) TAA (UGT1A1*28). 8/45 homozygous UGT1A1*28 cases were associated with additional pathogenic mutations causing hemolytic anemia, likely exacerbating hyperbilirubinemia. The most common mutated genes were membrane cytoskeleton genes SPTA1, and SPTB, followed by PKLR. Complex interactions between SPTA1 low expression alleles, alpha-LELY and alpha-LEPRA alleles, and intragenic SPTA1 variants were associated with hereditary pyropoikilocytosis and autosomal recessive hereditary spherocytosis in 23/111 patients.
CONCLUSIONS
Our results demonstrate that hemolytic anemia is underscored by complex molecular interactions of previously known and novel mutations in RBC cytoskeleton/enzyme genes, and therefore, NGS should be considered in all patients with clinically unexplained hemolytic anemia and in neonates with hyperbilirubinemia. Moreover, low expression alleles alpha-LELY and alpha-LEPRA should be included in all targeted HHA panels.
Topics: Humans; Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Spherocytosis, Hereditary; Cytoskeletal Proteins; Hyperbilirubinemia; High-Throughput Nucleotide Sequencing
PubMed: 36825813
DOI: 10.1111/ejh.13951 -
Georgian Medical News Nov 2019To illuminate modern ideas about Gilbert's syndrome (GS). GS is a common familial hyperbilirubinemia that can reduce the risk of various age-related diseases due to the... (Review)
Review
To illuminate modern ideas about Gilbert's syndrome (GS). GS is a common familial hyperbilirubinemia that can reduce the risk of various age-related diseases due to the antioxidant properties of bilirubin. In this case, slightly elevated unconjugated bilirubin in GS is strongly associated with a "reduced" prevalence of chronic diseases, in particular cardiovascular disease (CVD), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic byproduct of heme catabolism, and emphasize the importance of understanding its potential beneficial physiological and harmful pathophysiological effects. With this information, we hope to improve understanding of bilirubin metabolic disorders, highlight the diagnostic importance of these conditions, and map out the potential impact of GS on disease resistance.
Topics: Antioxidants; Bilirubin; Cardiovascular Diseases; Gilbert Disease; Humans
PubMed: 31889709
DOI: No ID Found -
Thorax Nov 2020
Topics: Bilirubin; Gilbert Disease; Humans; Lung Neoplasms
PubMed: 33023993
DOI: 10.1136/thoraxjnl-2020-215642 -
American Journal of Otolaryngology 2022While jaundice is frequently described in the sclera and skin, there are few reports of true vocal fold jaundice in patients with high bilirubin, and no reports by...
OBJECTIVES
While jaundice is frequently described in the sclera and skin, there are few reports of true vocal fold jaundice in patients with high bilirubin, and no reports by otolaryngologists in the literature. Here we describe a case of a patient with bilateral true vocal fold jaundice and discuss the potential pathogenesis and implications of this finding.
METHODS
A 29-year-old man with history of Dubin-Johnson Syndrome presented with cough and difficulty breathing and was incidentally found to have persistent yellow discoloration of the true vocal folds bilaterally.
RESULTS
Videolaryngoscopic exam demonstrated bilateral true vocal fold yellow discoloration with sparing of nearby laryngeal structures on initial presentation and follow-up exam. Direct and total bilirubin levels were found to be elevated.
CONCLUSION
A patient with benign Dubin-Johnson Syndrome and elevated total and direct bilirubin was incidentally found to have bilateral vocal fold jaundice. Jaundice and the presence of bilirubin do not appear to cause harm to the function or health of the true vocal folds and may be related to the high concentration of elastin present in the true vocal folds.
Topics: Adult; Bilirubin; Humans; Jaundice; Jaundice, Chronic Idiopathic; Liver Function Tests; Male; Vocal Cords
PubMed: 35417838
DOI: 10.1016/j.amjoto.2022.103456 -
The Journal of Physiology Apr 2022Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to...
Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1- C]-acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT-qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low-density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome). KEY POINTS: Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations. Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low-density lipoprotein (LDL) receptor expression. Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels. This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).
Topics: Animals; Bilirubin; Cholesterol; Female; Gilbert Disease; Hyperbilirubinemia; Hypercholesterolemia; Lipoproteins, LDL; Liver; Male; Rats; Rats, Gunn; Receptors, LDL; Sex Characteristics; Sterols
PubMed: 35156712
DOI: 10.1113/JP282395 -
Research and Practice in Thrombosis and... Oct 2022Neonatal-onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO...
BACKGROUND
Neonatal-onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility.
OBJECTIVE
To explore early indicators of neonatal-onset hTTP.
METHODS
This study was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups.
RESULTS
This study included four hTTP patients and 20 ABO-incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0-65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8-12.1) than ABO-incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO-incompatible newborns (odds ratio, 25.4; 95% CI, 1.2-551.6), and platelet counts were lower than in ABO-incompatible newborns (17 ± 12 × 10/L vs. 291 ± 76 × 10/L). The levels of serum creatinine (median difference, 51.8 μmol/L; 95% CI, 16.0-109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8-38.7) were higher in hTTP newborns than in ABO-incompatible newborns. There were no significant differences in white blood cell counts, C-reactive protein, alanine aminotransferase, or albumin levels.
CONCLUSIONS
Severe jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.
PubMed: 36254256
DOI: 10.1002/rth2.12820 -
Revista Espanola de Enfermedades... Aug 2021We present the case of a 35-year-old female with a history of polycystic ovary syndrome, treated with oral contraceptives. She was under study due to nine months...
We present the case of a 35-year-old female with a history of polycystic ovary syndrome, treated with oral contraceptives. She was under study due to nine months evolution of pain in the right iliac fossa, associated with hyporexia and mild hyperbilirubinemia with a predominance of the conjugated fraction (total Bi 3.7 mg/dl, conjugated Bi 2.9 mg/dl). An abdominal computed tomography (CT) was performed showing homogeneous hepatosplenomegaly and adenopathies in both iliac chains, the largest in the right external iliac chain of 1.6 x 3.6 cm.
Topics: Adult; Female; Humans; Hyperbilirubinemia; Jaundice, Chronic Idiopathic; Laparoscopy; Tomography, X-Ray Computed
PubMed: 33657825
DOI: 10.17235/reed.2021.7866/2021 -
Diagnostics (Basel, Switzerland) Aug 2021Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells... (Review)
Review
Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).
PubMed: 34573891
DOI: 10.3390/diagnostics11091549