A case of Gilbert syndrome (GS) with a heterozygous mutation in the gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. *28 and c.211G>A heterozygous mutations in gene were found, which may be another type of mutation causing GS in Chinese population.
Asian Continental Ancestry Group ; Bilirubin ; Gilbert Disease ; genetics ; Glucuronosyltransferase ; genetics ; Heterozygote ; Humans ; Mutation

BACKGROUND: Hyperbilirubinemia is a common postoperative complication. Elevated direct bilirubin (D-Bil) and indirect bilirubin (I-Bil) levels are related to different pathophysiologies; therefore, their associations with outcomes also differ. However, there have been few comparative studies of such associations in postoperative patients. METHODS: This retrospective study compared the associations of postoperative D-Bil and I-Bil with outcomes. We included adult patients requiring postoperative intensive care for more than 48 hours between 2008 and 2013, except those undergoing liver operations. The number of patients was determined using a power calculation. D-Bil and I-Bil measurements were obtained on postoperative days (POD) 1 and 2. The primary outcome was defined as hospital mortality, with the number of ICU-free survival days (IFSD) at POD 28 as the secondary outcome. RESULTS: The study population consisted of 1,903 patients with a mortality rate of 2.2%. D-Bil at POD 1 was significantly higher in non-survivors than survivors (P = 0.001), but I-Bil at POD 1 showed no such relation (P = 0.209). Multivariate logistic analysis indicated that higher postoperative D-Bil was independently associated with increased postoperative mortality (POD 1: adjusted odds ratio [OR] = 2.32, P < 0.001; POD 2: adjusted OR = 1.95, P < 0.001), but I-Bil showed no such relation (POD 1: P = 0.913; POD 2: P = 0.209). Increased D-Bil was independently associated with decreased IFSD at POD 28 (POD 1: adjusted coefficient = −1.54, P < 0.001; POD 2: −1.84, P < 0.001). In contrast, increased I-Bil at POD 1 was independently associated with increased IFSD at POD 28 (POD 1: adjusted coefficient = +0.39, P = 0.021; POD 2: +0.33, P = 0.080). CONCLUSIONS: D-Bil indices have a higher capability than I-Bil for predicting poorer outcomes in critically ill postoperative patients.
Adult ; Bilirubin ; Critical Care ; Critical Illness ; Gilbert Disease ; Hospital Mortality ; Humans ; Liver ; Mortality ; Odds Ratio ; Postoperative Complications ; Retrospective Studies ; Survivors

A two-year-old girl was admitted due to repeated yellowing of the skin and sclera for 2 years and had no other specific symptoms or signs. The use of phenobarbital could relieve the symptoms of jaundice. Multiple examinations showed increased indirect bilirubin levels, and the results of aminotransferases and liver imaging were normal. There was no evidence of hemolysis. The analysis of UGT1A1 gene in her family found that this child had double homozygous mutation of c.211G>A(G71R) and c.1456T>G(Y486D), which had been reported as the pathogenic mutation for Gilbert syndrome. Her parents carried double heterozygous mutation of G71R and Y486D and had no symptom of jaundice. The child was diagnosed as having Gilbert syndrome. It is concluded that as for patients with unconjugated hyperbilirubinemia which cannot be explained by liver damage and hemolysis, their family history should be investigated in detail and gene analysis should be performed as early as possible, in order to identify congenital bilirubin metabolic disorders.
Child, Preschool ; Female ; Gilbert Disease ; diagnosis ; Glucuronosyltransferase ; genetics ; Humans ; Mutation ; Sclera ; pathology ; Skin ; pathology

OBJECTIVETo explore the clinical features and gene mutation profiles of patients with chronic hepatitis B (CHB) and Gilbert's syndrome.

METHODSThirty-three patients with CHB and Gilbert's syndrome were enrolled in the study. Serum markers of liver function and histological features of disease-related liver injury were assessed by standard methods. Gene mutations were detected by PCR and direct DNA sequencing.Statistical analysis was carried out with the chi-square and t tests.

RESULTSSequencing of the Gilbert syndrome-associated gene, UGT 1A 1, revealed mutations in the upstream promoter phenobarbital-responsive element module (PBREM) (-3279 mutation, 23 cases), in the promoter TATA box (a TA insertion mutation, 21 cases), and in the coding region of exon 1 (a GGA-AGA Gly71Arg mutation, 18 cases); there was no statistical difference found for any of the three mutations among this patient population (x2 =1.640, P more than 0.05).

CONCLUSIONThe traditional methods of diagnosis for patients with CHB and Gilbert's syndrome remain a technical challenge in the clinic, and gene detection may represent a more favorable method for diagnosing this patient population.

Base Sequence ; Exons ; Gilbert Disease ; Glucuronosyltransferase ; Hepatitis B, Chronic ; Humans ; Mutagenesis, Insertional ; Mutation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; TATA Box

Gilbert Disease ; Hemochromatosis ; Humans

Gilbert syndrome is the most common inherited disorder of bilirubin glucuronidation. It is characterized by intermittent episodes of jaundice in the absence of hepatocellular disease or hemolysis. Hereditary spherocytosis is the most common inherited hemolytic anemia and is characterized by spherical, osmotically fragile erythrocytes that are selectively trapped by the spleen. The patients have variable degrees of anemia, jaundice, and splenomegaly. Hereditary spherocytosis usually leads to mild-to-moderate elevation of serum bilirubin levels. Severe hyperbilirubinemia compared with the degree of hemolysis should be lead to suspicion of additional clinical conditions such as Gilbert syndrome or thalassemia. We present the case of a 12-year-old boy with extreme jaundice and nausea. The diagnosis of hereditary spherocytosis was confirmed by osmotic fragility test results and that of Gilbert syndrome by genetic analysis findings.
Anemia ; Anemia, Hemolytic ; Bilirubin ; Child* ; Diagnosis ; Erythrocytes ; Gilbert Disease* ; Hemolysis ; Humans ; Hyperbilirubinemia ; Jaundice* ; Male ; Nausea ; Osmotic Fragility ; Spleen ; Splenomegaly ; Thalassemia

We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.
Adult ; Erythrocytes/physiology ; Gallstones/etiology ; Genotype ; Gilbert Disease/complications/*diagnosis/genetics ; Glucuronosyltransferase/genetics ; Hemolysis ; Humans ; Hyperbilirubinemia/etiology ; Male ; Polymorphism, Single Nucleotide ; Spherocytosis, Hereditary/complications/*diagnosis/genetics ; Splenomegaly/etiology

OBJECTIVETo explore the pathological characteristics of inborn hyperbilirubinemia of patients with Gilbert's syndrome (GS).

METHODSPatients with GS (n = 7) and patients with chronic hepatitis B (CHB; n = 8) were enrolled in the study. GS was diagnosed by peripheral blood analysis results showing glucuronyl transferase gene mutation. The histology and ultrastructure of biopsied liver tissues were evaluated by light microscopy and transmission electron microscopy.

RESULTSThe GS group showed normal structure in the hepatic portal area and lobule; however, bile pigment granules with high electron density were noted in the hepatocytes. The CHB group showed abnormal structure of the hepatic lobules, including infiltration of inflammatory cells, necrotic regions, degenerated hepatocytes, bile duct injury, and fibrosis in the portal tracts; a few bile pigment granules were observed. The GS group also showed greater quantity and size of bilirubin deposits than the CHB group.

CONCLUSIONThe histological and ultrastructural features of GS include normal hepatic lobule and deposition of bile pigment granules in hepatocytes.

Adolescent ; Adult ; Child ; Female ; Gilbert Disease ; pathology ; Hepatitis B, Chronic ; pathology ; Hepatocytes ; ultrastructure ; Humans ; Liver ; cytology ; pathology ; Male ; Young Adult

Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC beta isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications.
Angiotensin II ; Antioxidants ; Bilirubin ; Biliverdine ; Chymases ; Diabetic Angiopathies ; Gilbert Disease ; Glucagon-Like Peptide 1 ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperbilirubinemia ; Inflammation ; NADPH Oxidase ; Oxidative Stress ; Oxidoreductases ; Prevalence ; Protein Kinase C ; Reactive Oxygen Species ; Receptors, Angiotensin ; Up-Regulation

PURPOSE: This study aims to reveal more effective clinical or laboratory markers for the diagnosis of acute appendicitis and to score the severity based on a sufficiently large number of patients with acute appendicitis. METHODS: We identified 1,195 patients with acute appendicitis after excluding those with other causes of hyperbilirubinemia among the 1,271 patients that underwent a laparoscopic or an open appendectomy between 2009 and 2010. A retrospective chart review of the medical records, including laboratory and histologic results, was conducted. We then analyzed the data using univariate and multivariate analyses. RESULTS: Among the 1,195 patients, a laparoscopic appendectomy was performed in 685 cases (57.32%), and an open appendectomy was performed in 510 cases (42.68%). The univariate analysis demonstrated significant differences for white blood cell count (P < 0.0001), segmented neutrophils (P = 0.0035), total bilirubin (P < 0.0001), and systemic inflammatory response syndrome (SIRS) score between groups (P < 0.0001). The multivariate analysis demonstrated that total bilirubin (odds ratio, 1.772; 95% confidence interval, 1.320 to 2.379; P = 0.0001) and SIRS score (odds ratio, 1.583; 95% confidence interval, 1.313 to 1.908; P < 0.0001) have statistically significant diagnostic value for perforated appendicitis. CONCLUSION: Hyperbilirubinemia is a statistically significant diagnostic marker for acute appendicitis and the likelihood of perforation.
Appendectomy ; Appendicitis ; Bilirubin ; Biomarkers ; Gilbert Disease ; Humans ; Hyperbilirubinemia ; Leukocyte Count ; Medical Records ; Multivariate Analysis ; Neutrophils ; Retrospective Studies ; Systemic Inflammatory Response Syndrome