607 results match your criteria Crigler-Najjar Syndrome


[Analysis of mutation site characteristics of Gilbert syndrome and Crigler--Najjar syndrome in relation to uridine diphosphate glucuronosyltransferase A1 gene].

Zhonghua Gan Zang Bing Za Zhi 2020 May;28(5):428-433

Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069,China; Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069,China.

To investigate the mutation characteristics and clinical relevance of Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1) gene. The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases. A total of 163 mutation sites were found in the UGT1A1 gene since November 16, 2018. Read More

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http://dx.doi.org/10.3760/cma.j.cn501113-20200217-00051DOI Listing

Induction of fecal cholesterol excretion is not effective for the treatment of hyperbilirubinemia in Gunn rats.

Pediatr Res 2020 May 1. Epub 2020 May 1.

Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Background: Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. Read More

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http://dx.doi.org/10.1038/s41390-020-0926-2DOI Listing

Diffusion Tensor Imaging of Microstructural Changes in the Gray and White Matter in Patients With Crigler-Najjar Syndrome Type I.

J Comput Assist Tomogr 2020 May/Jun;44(3):393-398

Neurology Unit of Mansoura Children Hospital, Mansoura Faculty of Medicine, Mansoura, Egypt.

Purpose: This study aimed to evaluate the role of diffusion tensor imaging of microstructural changes in gray and white matter in Crigler-Najjar syndrome type I.

Patient And Methods: A prospective study was conducted on 10 patients with Crigler-Najjar syndrome type I and 10 age- and sex-matched children who underwent diffusion tensor imaging of the brain. Mean diffusivity (MD) and fractional anisotropy (FA) of gray and white matter were measured. Read More

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http://dx.doi.org/10.1097/RCT.0000000000001008DOI Listing
May 2020
1.602 Impact Factor

Variants c.864+5G>T and c.996+2_996+5del of a Crigler-Najjar Patient Induce Aberrant Splicing in Minigene Assays.

Front Genet 2020 6;11:169. Epub 2020 Mar 6.

Splicing and Genetic Susceptibility to Cancer, Instituto de Biología y Genética Molecular (CSIC-UVa), Valladolid, Spain.

A large fraction of DNA variants impairs pre-mRNA splicing in human hereditary disorders. Crigler-Najjar syndrome (CNS) is characterized by a severe unconjugated hyperbilirubinemia caused by variants in the gene. We previously reported one CNS-type II patient with two splice-site variants in trans (c. Read More

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http://dx.doi.org/10.3389/fgene.2020.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067894PMC

A case report of a novel 22 bp duplication within exon 1 of the UGT1A1 in a Sudanese infant with Crigler-Najjar syndrome type I.

BMC Gastroenterol 2020 Mar 6;20(1):62. Epub 2020 Mar 6.

Department of Molecular Diagnostics, Genes N Life Healthcare Pvt. Ltd., Punjagutta, Hyderabad, 500 082, India.

Background: Crigler Najjar type 1 is a rare autosomal recessive condition caused by the absence of UDPGT enzyme due to mutations in the UGT1A1 gene. This enzyme is responsible for elimination of unconjugated bilirubin from the body by glucuronidation. Affected individuals are at risk for kernicterus and require lifelong phototherapy. Read More

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http://dx.doi.org/10.1186/s12876-020-01192-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060512PMC
March 2020
2.365 Impact Factor

Carbon monoxide breath test assessment of mild hemolysis in Gilbert's syndrome.

Medicine (Baltimore) 2020 Feb;99(7):e19109

Department of Gastroenterology, Nanshan Hospital, Guangdong Medical University.

Background: Mild hemolysis is difficult to determinate by traditional methods, and its role in Gilbert's syndrome (GS) is unclear. The main aims were to inspect the erythrocyte (RBC) survival in GS by using Levitt's carbon monoxide (CO) breath test and to assess its contribution to unconjugated hyperbilirubinemia.

Methods: Fifty subjects with GS and 1 with type-II Crigler-Najjar syndrome (CN2) received RBC lifespan measurement with Levitt's CO breath test. Read More

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http://dx.doi.org/10.1097/MD.0000000000019109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035016PMC
February 2020

Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice.

Sci Rep 2020 Jan 21;10(1):887. Epub 2020 Jan 21.

Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.

Crigler Najjar Syndrome type I (CNSI) is a rare recessive disorder caused by mutations in the Ugt1a1 gene. There is no permanent cure except for liver transplantation, and current therapies present several shortcomings. Since stem cell-based therapy offers a promising alternative for the treatment of this disorder, we evaluated the therapeutic potential of human liver stem cells (HLSC) in immune-compromised NOD SCID Gamma (NSG)/Ugt1 mice, which closely mimic the pathological manifestations in CNSI patients. Read More

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http://dx.doi.org/10.1038/s41598-020-57820-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972964PMC
January 2020

Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier.

Hepatology 2020 Jun 5;71(6):1923-1939. Epub 2020 Feb 5.

Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.

Background And Aims: We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years.

Approach And Results: Unbound ("free") bilirubin (B ) was measured in patient sera to characterize the binding of unconjugated bilirubin (B ) to albumin (A) and validate their molar concentration ratio (B /A) as an index of neurological risk. Read More

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http://dx.doi.org/10.1002/hep.30959DOI Listing
June 2020
2 Reads

Prevalence and Relevance of Pre-Existing Anti-Adeno-Associated Virus Immunity in the Context of Gene Therapy for Crigler-Najjar Syndrome.

Hum Gene Ther 2019 10;30(10):1297-1305

Genethon, Evry, France.

Adeno-associated virus (AAV) vector-mediated gene therapy is currently evaluated as a potential treatment for Crigler-Najjar syndrome (CN) (NCT03466463). Pre-existing immunity to AAV is known to hinder gene transfer efficacy, restricting enrollment of seropositive subjects in ongoing clinical trials. We assessed the prevalence of anti-AAV serotype 8 (AAV8) neutralizing antibodies (NAbs) in subjects affected by CN and investigated the impact of low NAb titers (<1:5) on liver gene transfer efficacy in an passive immunization model. Read More

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http://dx.doi.org/10.1089/hum.2019.143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763963PMC
October 2019
1 Read

Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives.

J Gastroenterol Hepatol 2020 Apr 24;35(4):530-543. Epub 2019 Oct 24.

Audentes Therapeutics, San Francisco, CA, USA.

Background And Aim: Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.

Methods: A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS. Read More

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http://dx.doi.org/10.1111/jgh.14853DOI Listing
April 2020
7 Reads

Domino liver transplantation for select metabolic disorders: Expanding the living donor pool.

JIMD Rep 2019 Jul 19;48(1):83-89. Epub 2019 Jun 19.

Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine Pittsburgh Pennsylvania.

Domino liver transplantation (DLT) involves transplanting liver from a patient with metabolic disease into a patient with end-stage liver disease with the expectation that the recipient will not develop the metabolic syndrome or the recurrent syndrome will have minimal affect. The domino donor gets a deceased donor or a segment of live-donor liver through the deceased donor organ allocation system. Waitlist mortality for the domino recipient exceeds morbidity associated with getting the donor disease. Read More

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http://dx.doi.org/10.1002/jmd2.12053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606984PMC
July 2019
4 Reads

Regenerative cell therapy for the treatment of hyperbilirubinemic Gunn rats with fresh and frozen human induced pluripotent stem cells-derived hepatic stem cells.

Xenotransplantation 2020 Jan 25;27(1):e12544. Epub 2019 Jul 25.

INSERM, UMRS 1064-Center for Research in Transplantation and Immunology, Nantes, France.

Pluripotent stem cells have been investigated as a renewable source of therapeutic hepatic cells, in order to overcome the lack of transplantable donor hepatocytes. Whereas different studies were able to correct hepatic defects in animal models, they focused on the most mature phenotype of hepatocyte-like cells (HLCs) derived from pluripotent stem cells and needed freshly prepared cells, which limits clinical applications of HLCs. Here, we report the production of hepatic stem cells (pHSCs) from human-induced pluripotent stem cells (hiPSCs) in xeno-free, feeder-free, and chemically defined conditions using as extracellular matrix a recombinant laminin instead of Matrigel, an undefined animal-derived matrix. Read More

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http://dx.doi.org/10.1111/xen.12544DOI Listing
January 2020
5 Reads

UGT1A1 mutations and psychoses: towards understanding the relationship with unconjugated bilirubin.

CNS Spectr 2019 Jul 24:1-3. Epub 2019 Jul 24.

School of Medicine and Surgery, University of Milano-Bicocca,Monza,Italy.

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http://dx.doi.org/10.1017/S1092852919001251DOI Listing
July 2019
4 Reads

A novel deletion with two pathogenic variants of UGT1A1 causing Crigler-Najjar syndrome in two unrelated Chinese.

Clin Biochem 2019 Sep 24;71:67-68. Epub 2019 Jun 24.

Institutes of Biomedical Sciences and Children's Hospital of Fudan University, Shanghai 200032, PR China. Electronic address:

Two Chinese female infants from two unrelated families were diagnosed with Crigler-Najjar syndromes-I (CNS-I) and CNS-II respectively. The CNS-I patient had Serum Total Bilirubin Concentration (STBC) peaked at 26.1 mg/dL. Read More

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http://dx.doi.org/10.1016/j.clinbiochem.2019.06.013DOI Listing
September 2019
6 Reads

Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias.

Clin Biochem 2019 Jul 27;69:30-35. Epub 2019 May 27.

Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address:

Inherited unconjugated hyperbilirubinemias are a group of disorders characterized by increased levels of serum unconjugated bilirubin and arise because of the imbalance between its production and elimination from the body. It includes Crigler-Najjar syndrome and Gilbert syndrome. Crigler-Najjar syndrome type 1 represents the extreme severe end of the spectrum with complete absence of hepatic bilirubin uridine diphosphoglucuronate glucuronosyltransferase (UGT1A1). Read More

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http://dx.doi.org/10.1016/j.clinbiochem.2019.05.012DOI Listing
July 2019
33 Reads
2.229 Impact Factor

A novel UGT1A1 gene mutation causing severe unconjugated hyperbilirubinemia: a case report.

BMC Pediatr 2019 05 29;19(1):173. Epub 2019 May 29.

Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Meibergdreef 69-71, 1105 BK, Amsterdam, The Netherlands.

Background: Crigler-Najjar syndrome (CNs) presents as unconjugated hyperbilirubinemia, as a result of UGT1A1 deficiency, and can be categorized in a severe (type I) and mild (type II) phenotype. CNs type II patients usually benefit from phenobarbital treatment that induces residual UGT1A1 activity.

Case Presentation: Here we present a CNs type II patient that is not responsive to phenobarbital treatment, which can be explained by two heterozygous mutations in the UGT1A1 gene. Read More

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http://dx.doi.org/10.1186/s12887-019-1555-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540546PMC
May 2019
36 Reads

Ultrasound-guided in Utero Transplantation of Placental Stem Cells into the Liver of Crigler-Najjar Syndrome Model Rat.

Transplantation 2019 07;103(7):e182-e187

Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing. Read More

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http://dx.doi.org/10.1097/TP.0000000000002735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594893PMC
July 2019
6 Reads

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients.

Transplantation 2019 09;103(9):1903-1915

Department of Paediatrics, Paediatric Gastroenterology and Hepatology Unit, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.

Background: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Objective: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Read More

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http://dx.doi.org/10.1097/TP.0000000000002605DOI Listing
September 2019
41 Reads

Preclinical Development of an AAV8-hUGT1A1 Vector for the Treatment of Crigler-Najjar Syndrome.

Mol Ther Methods Clin Dev 2019 Mar 31;12:157-174. Epub 2018 Dec 31.

INTEGRARE, Genethon, INSERM, Univ. Evry, Université Paris-Saclay, 91002 Evry, France.

Adeno-associated viruses (AAVs) are among the most efficient vectors for liver gene therapy. Results obtained in the first hemophilia clinical trials demonstrated the long-term efficacy of this approach in humans, showing efficient targeting of hepatocytes with both self-complementary (sc) and single-stranded (ss) AAV vectors. However, to support clinical development of AAV-based gene therapies, efficient and scalable production processes are needed. Read More

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http://dx.doi.org/10.1016/j.omtm.2018.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348934PMC
March 2019
12 Reads

[Study on spectrum of UGT1A1 mutations in connection with inherited non-hemolytic unconjugated hyperbilirubinemia].

Zhonghua Gan Zang Bing Za Zhi 2018 Dec;26(12):898-902

Liver Disease Department, Nanjing Second Hospital, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China.

To compare and analyze patient's general condition, changes in laboratory parameters, and the spectrum of UGT1A1 mutations in patients with inherited non-hemolytic unconjugated hyperbilirubinemia. A retrospective study was conducted at Nanjing Second Hospital from January 2015 to July 2018 and patients' demographic characteristics, liver function test, and UGT1A1 gene were analyzed. The categorical variable data were compared by (2) test. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2018.12.005DOI Listing
December 2018
35 Reads

[Clinical and pathological features of inherited metabolic liver disease in adults].

Authors:
Z Y He H You X Y Zhao

Zhonghua Gan Zang Bing Za Zhi 2018 Dec;26(12):889-893

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Inherited metabolic liver disease is a kind of metabolic disorders caused by the interactions between host and environmental factors because of genetic defects. The incidence of inherited metabolic liver disease is low and its clinical manifestations are complex and diverse, which initiates difficulties in clinical diagnosis. In addition, hereditary hemochromatosis and Wilson's disease are common types of metabolic abnormalities, often seem in clinical practice, and early diagnosis and treatment can improve the prognosis. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2018.12.003DOI Listing
December 2018
6 Reads

Genes and Pathways Promoting Long-Term Liver Repopulation by hYAP-ERT2 Transduced Hepatocytes and Treatment of Jaundice in Gunn Rats.

Hepatol Commun 2019 Jan 20;3(1):129-146. Epub 2018 Nov 20.

Department of Medicine Marion Bessin Liver Research Center, Albert Einstein College of Medicine Bronx NY.

Hepatocyte transplantation is an attractive alternative to liver transplantation. Thus far, however, extensive liver repopulation by adult hepatocytes has required ongoing genetic, physical, or chemical injury to host liver. We hypothesized that providing a regulated proliferative and/or survival advantage to transplanted hepatocytes should enable repopulation in a normal liver microenvironment. Read More

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http://dx.doi.org/10.1002/hep4.1278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312667PMC
January 2019
28 Reads

AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.

Mol Ther Methods Clin Dev 2018 Dec 5;11:191-201. Epub 2018 Dec 5.

Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1. Read More

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http://dx.doi.org/10.1016/j.omtm.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282099PMC
December 2018
9 Reads

UGT1A1 genotypes and unconjugated hyperbilirubinemia phenotypes in post-neonatal Chinese children: A retrospective analysis and quantitative correlation.

Medicine (Baltimore) 2018 Dec;97(49):e13576

Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China.

To retrospectively analyze and quantitatively correlate UGT1A1 (bilirubin UDP- glucuronosyltransferase gene) genotypes and unconjugated hyperbilirubinemia (UCH) phenotypes among Chinese children.We retrospectively reviewed UCH patients, quantitatively analyzed genotype-phenotype correlation by comparing with healthy controls. Pfam database, SWISS-model, and Pymol were used for UGT1A1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on protein structure. Read More

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http://dx.doi.org/10.1097/MD.0000000000013576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310575PMC
December 2018
12 Reads

A Novel Pathogenic Variant in a Sudanese Child with Type 1 Crigler-Najjar Syndrome.

Drug Metab Dispos 2019 01 1;47(1):45-48. Epub 2018 Nov 1.

Department of Pediatrics, Milton S. Hershey Penn State Medical Center, Hershey, Pennsylvania (W.E.); Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Helsinki, Finland (E.J., J.M., M.F.); Pediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut (W.J., A.G.S., M.K., S.A.L.); Departments of Pathology and Cell Biology (A.C.I.) and Surgery (S.J.L.), Columbia University Medical Center, New York, New York; and Department of Pediatrics, University of Rochester Medical Center, Rochester, New York (A.C.)

Uridine diphosphate glucuronosyltransferases (UGTs) are key enzymes responsible for the body's ability to process a variety of endogenous and exogenous compounds. Significant gains in understanding UGT function have come from the analysis of variants seen in patients. We cared for a Sudanese child who showed clinical features of type 1 Crigler-Najjar syndrome (CN-1), namely severe unconjugated hyperbilirubinemia leading to liver transplantation. Read More

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http://dmd.aspetjournals.org/lookup/doi/10.1124/dmd.118.0843
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http://dx.doi.org/10.1124/dmd.118.084368DOI Listing
January 2019
12 Reads

Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience.

JIMD Rep 2019 12;45:29-36. Epub 2018 Oct 12.

Institute of Liver Disease and Transplantation, Gleneagles Global Health City, Chennai, India.

Purpose: Auxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression.

Methods: Retrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD.

Results: A total of 13 APOLT procedures were performed for MLD during the study period. Read More

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http://link.springer.com/10.1007/8904_2018_137
Publisher Site
http://dx.doi.org/10.1007/8904_2018_137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336549PMC
October 2018
69 Reads

Case report: multiple UGT1A1 gene variants in a patient with Crigler-Najjar syndrome.

BMC Pediatr 2018 10 3;18(1):317. Epub 2018 Oct 3.

Scientific Laboratory of Molecular Genetics, Riga Stradiņš University, Dzirciema Street 16, Riga, LV 1007, Latvia.

Background: Inherited unconjugated hyperbilirubinemia is caused by variants in the gene UGT1A1 leading to Gilbert's syndrome and Crigler-Najjar syndrome types I and II. These syndromes are differentiated on the basis of UGT1A1 residual enzymatic activity and its affected bilirubin levels and responsiveness to phenobarbital treatment.

Case Presentation: In this report, we present a boy with Crigler-Najjar syndrome type II with high unconjugated bilirubin levels that decreased after phenobarbital treatment but increased in adolescence. Read More

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https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887
Publisher Site
http://dx.doi.org/10.1186/s12887-018-1285-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169020PMC
October 2018
11 Reads

Transplanted Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Support Liver Regeneration in Gunn Rats.

Stem Cells Dev 2018 12 20;27(24):1702-1714. Epub 2018 Nov 20.

Institute for Stem Cell Research and Regenerative Medicine, Neonatolgy and Pediatric Cardiology, Heinrich Heine University, Düsseldorf, Germany.

Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 () gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. Read More

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https://www.liebertpub.com/doi/10.1089/scd.2018.0010
Publisher Site
http://dx.doi.org/10.1089/scd.2018.0010DOI Listing
December 2018
24 Reads

Crigler-Najjar Syndrome Type II Diagnosed in a Patient with Jaundice Since Birth.

J Coll Physicians Surg Pak 2018 Oct;28(10):806-808

Department of Medicine, King Edward Medical University, Lahore, Pakistan.

Crigler-Najjar syndrome type II is caused by mutations in the UGT1A1 gene resulting in severely reduced hepatic activity of UDP-glucoronyltransferase - an enzyme required to convert bilirubin into a more soluble form that can then be removed from the body. Absence or severe deficiency of this enzyme can lead to bilirubin accumulation in the body resulting in yellow skin and eyes (jaundice). The earliest signs of this disease can be apparent in the neonatal period. Read More

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http://dx.doi.org/3028DOI Listing
October 2018
12 Reads
0.318 Impact Factor

Liver Cirrhosis in a Patient with Crigler Najjar Syndrome.

Fetal Pediatr Pathol 2018 Aug 27;37(4):301-306. Epub 2018 Sep 27.

c Department of Pathology , Baskent University Faculty of Medicine , Ankara , Turkey.

Introduction: Crigler Najjar (CN) disease is a genetic disorder which results in increased unconjugated bilirubin level. Liver parenchyma was previously considered structurally normal. Recent reports describe significant fibrosis in the liver parenchyma of patients with CN syndrome. Read More

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http://dx.doi.org/10.1080/15513815.2018.1492053DOI Listing
August 2018
11 Reads

Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome.

Mol Ther Methods Clin Dev 2018 Sep 21;10:237-244. Epub 2018 Jul 21.

Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) activity. This syndrome is characterized by hyperbilirubinemia and jaundice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23290501183007
Publisher Site
http://dx.doi.org/10.1016/j.omtm.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090885PMC
September 2018
39 Reads

Neuro-inflammatory effects of photodegradative products of bilirubin.

Sci Rep 2018 05 10;8(1):7444. Epub 2018 May 10.

Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

Phototherapy was introduced in the early 1950's, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight (ELBW) infants. Read More

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http://dx.doi.org/10.1038/s41598-018-25684-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945592PMC
May 2018
4 Reads

Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand.

J Pediatr Genet 2018 Jun 16;7(2):67-73. Epub 2018 Feb 16.

Pediatric Surgery Unit, Department of Surgery, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. Read More

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http://dx.doi.org/10.1055/s-0038-1632395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916803PMC
June 2018
21 Reads

Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1.

CPT Pharmacometrics Syst Pharmacol 2018 06 26;7(6):404-412. Epub 2018 Apr 26.

Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA.

Crigler-Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine-diphosphate-glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1-modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first-in-human studies, a quantitative systems pharmacology (QSP) model was developed. Read More

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http://doi.wiley.com/10.1002/psp4.12301
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http://dx.doi.org/10.1002/psp4.12301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391595PMC
June 2018
27 Reads

AAV8 Gene Therapy Rescues the Newborn Phenotype of a Mouse Model of Crigler-Najjar.

Hum Gene Ther 2018 07;29(7):763-770

Gene Therapy Program, Department of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.

Adeno-associated viral (AAV) vectors can target the liver, making them an attractive platform for gene therapy approaches that require the correction of hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of bilirubin metabolism that occurs when the liver's uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely absent. This syndrome is characterized by elevated bilirubin levels in the blood. Read More

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http://dx.doi.org/10.1089/hum.2017.185DOI Listing
July 2018
9 Reads

Severe Neonatal Hyperbilirubinemia in Crigler-Najjar Syndrome Model Mice Can Be Reversed With Zinc Protoporphyrin.

Hepatol Commun 2017 Oct 10;1(8):792-802. Epub 2017 Aug 10.

Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, CA.

Neurotoxic bilirubin is solely conjugated by UDP-glucuronosyltransferase (UGT) 1A1. Due to an inadequate function of UGT1A1, human neonates develop mild to severe physiological hyperbilirubinemia. Accumulation of bilirubin in the brain leads to the onset of irreversible brain damage called kernicterus. Read More

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http://doi.wiley.com/10.1002/hep4.1082
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http://dx.doi.org/10.1002/hep4.1082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678921PMC
October 2017
13 Reads

Diagnostic criteria and contributors to Gilbert's syndrome.

Crit Rev Clin Lab Sci 2018 03 1;55(2):129-139. Epub 2018 Feb 1.

b School of Medical Science and Menzies Health Institute Queensland , Griffith University , Gold Coast , Australia.

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Read More

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http://dx.doi.org/10.1080/10408363.2018.1428526DOI Listing
March 2018
31 Reads

Crigler-Najjar Syndrome: Current Perspectives and the Application of Clinical Genetics.

Endocr Metab Immune Disord Drug Targets 2018 ;18(3):201-211

Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Crigler-Najjar syndrome (CNS, OMIM: 218800) is the paradigm of an inborn error of metabolism and a rare genetic disease with an estimated incidence of 0.6-1.0 per million live births. Read More

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http://dx.doi.org/10.2174/1871530318666171213153130DOI Listing
September 2018
5 Reads

Hepatic Parenchymal Injury in Crigler-Najjar Type I.

J Pediatr Gastroenterol Nutr 2018 04;66(4):588-594

Division of Gastroenterology, Hepatology and Nutrition.

Background: Crigler-Najjar syndrome type I (CNI) arises from biallelic variants of UGT1A1 that abrogate uridine diphosphate glucuronosyltransferase (UGT1A1) activity resulting in unconjugated hyperbilirubinemia. Historically, liver parenchyma in CNI was considered structurally and histologically normal. Recent review of CNI liver explants revealed fibrosis. Read More

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http://dx.doi.org/10.1097/MPG.0000000000001843DOI Listing
April 2018
9 Reads

Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II.

Medicine (Baltimore) 2017 Nov;96(45):e8620

Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.

Diagnosis of Crigler-Najjar syndrome type II (CNS-II) and Gilbert syndrome (GS) based on the serum bilirubin concentration is difficult, because this parameter can fluctuate under certain conditions. The aim of this study was to explore differences in UGT1A1 gene mutations, which cause both CNS and GS, and pathological changes between CNS-II and GS.Ninety-five Chinese patients with hereditary unconjugated hyperbilirubinemia were enrolled in this study. Read More

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http://dx.doi.org/10.1097/MD.0000000000008620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690788PMC
November 2017
34 Reads

UGT1A1 gene linkage analysis: application of polymorphic markers rs4148326/rs4124874 in the Iranian population.

Iran J Basic Med Sci 2017 Aug;20(8):880-885

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Objectives: Mutations in the UGT1A1 gene are responsible for hyperbilirubinemia syndromes including Crigler-Najjar type 1 and 2 and Gilbert syndrome. In view of the genetic heterogeneity and involvement of large numbers of the disease causing mutations, the application of polymorphic markers in the UGTA1 gene could be useful in molecular diagnosis of the disease.

Materials And Methods: In the present study, two polymorphic markers including rs4148326 and rs4124874 in the UGT1A1 gene region were characterized. Read More

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http://ijbms.mums.ac.ir/article_9109.html
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http://dx.doi.org/10.22038/IJBMS.2017.9109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651473PMC
August 2017
10 Reads

Crigler Najjar Syndrome Type 2 (CNS Type 2): An Unwonted Cause of Jaundice in Adults.

J Clin Diagn Res 2017 Jul 1;11(7):OD05-OD06. Epub 2017 Jul 1.

Consultant, Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi, India.

Crigler Najjar Syndrome (CNS) Type 2 is an uncommon genetic disorder characterised by non-haemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase- 1, required for the conjugation and further excretion of bilirubin from the body. Affected individuals are usually asymptomatic apart from the jaundice and investigations reveal isolated indirect hyperbilirubinemia. Read More

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http://jcdr.net/article_fulltext.asp?issn=0973-709x&year
Publisher Site
http://dx.doi.org/10.7860/JCDR/2017/28195.10221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583863PMC
July 2017
24 Reads

Repeated AAV-mediated gene transfer by serotype switching enables long-lasting therapeutic levels of hUgt1a1 enzyme in a mouse model of Crigler-Najjar Syndrome Type I.

Gene Ther 2017 10 14;24(10):649-660. Epub 2017 Aug 14.

Mouse Molecular Genetics, Molecular Medicine and Cellular Immunology Groups, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

Adeno-associated virus (AAV) -mediated gene therapy is a promising strategy to treat liver-based monogenic diseases. However, two major obstacles limit its success: first, vector dilution in actively dividing cells, such as hepatocytes in neonates/children, due to the non-integrating nature of the vector; second, development of an immune response against the transgene and/or viral vector. Crigler-Najjar Syndrome Type I is a rare monogenic disease with neonatal onset, caused by mutations in the liver-specific UGT1 gene, with toxic accumulation of unconjugated bilirubin in plasma, tissues and brain. Read More

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http://www.nature.com/doifinder/10.1038/gt.2017.75
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http://dx.doi.org/10.1038/gt.2017.75DOI Listing
October 2017
57 Reads

Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model.

EMBO Mol Med 2017 10;9(10):1346-1355

International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

Crigler-Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an gene targeting approach based on the insertion, without the use of nucleases, of a promoterless therapeutic cDNA into the albumin locus of a mouse model reproducing all major features of CNSI Neonatal transduction with the donor vector resulted in the complete rescue from neonatal lethality, with a therapeutic reduction in plasma bilirubin lasting for at least 12 months, the latest time point analyzed. Read More

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http://dx.doi.org/10.15252/emmm.201707601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623861PMC
October 2017
60 Reads

Liver Fibrosis Associated With Crigler-Najjar Syndrome in a Compound Heterozygote: A Case Report.

Pediatr Dev Pathol 2017 Nov-Dec;20(6):522-525. Epub 2017 Mar 14.

1 Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Crigler-Najjar syndrome is a hereditary unconjugated hyperbilirubinemia. Two forms of the disease are recognized. Type I is more severe and results in kernicterus if left untreated, and Type II is less severe and responds to phenobarbital. Read More

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http://dx.doi.org/10.1177/1093526617697059DOI Listing
May 2019
50 Reads

Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1 mouse model.

J Neuroinflammation 2017 03 24;14(1):64. Epub 2017 Mar 24.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 99, 34149, Trieste, Italy.

Background: Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced neurological damage and eventually death by kernicterus. Bilirubin neurotoxicity is characterized by a wide array of neurological deficits, including irreversible abnormalities in motor, sensitive and cognitive functions, due to bilirubin accumulation in the brain. Read More

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http://dx.doi.org/10.1186/s12974-017-0838-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366125PMC
March 2017
30 Reads

UGT1A1 polymorphisms in cancer: impact on irinotecan treatment.

Pharmgenomics Pers Med 2017 28;10:61-68. Epub 2017 Feb 28.

Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, Japan.

Mutations in the gene have been implicated in Gilbert syndrome, which shows mild hyperbilirubinemia, and a more aggressive childhood subtype, Crigler-Najjar syndrome. To date, more than 100 variants have been found in the gene. Among them, and have been reported to be associated with severe toxicities in patients treated with irinotecan-based chemotherapy by increasing the dose of SN-38 (7-ethyl-10-hydroxycamptothecin), an active form of irinotecan. Read More

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http://dx.doi.org/10.2147/PGPM.S108656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338934PMC
February 2017
18 Reads