621 results match your criteria Crigler-Najjar Syndrome


-related Bilirubin Encephalopathy/Kernicterus in Adults.

J Clin Transl Hepatol 2021 Apr 11;9(2):180-186. Epub 2021 Mar 11.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.

Background And Aims: Bilirubin encephalopathy/kernicterus is very rare in adults. This study is aimed to investigate the clinical manifestations and genetic features of two patients with -related kernicterus.

Methods: Sanger sequencing analysis was performed to identify gene mutations in the patients and their families. Read More

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The First Two Liver Transplantations in Syria.

Authors:
Fadi Rayya

Case Rep Gastroenterol 2021 Jan-Apr;15(1):296-304. Epub 2021 Mar 11.

General and HPB Surgery, Al Assad University Hospital, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic.

Liver transplantation (LT) is the only curative therapy for the end-stage liver diseases and some metabolic disorders which affect the hepatic cell like the Crigler-Najjar syndrome type 1 (CNSI). Although the LT is a routine procedure in many centers worldwide, the postoperative complications such as rejection, arterial thrombosis, and infection remain serious challenges even in big centers. In our paper, we demonstrate the first two LTs in Syria. Read More

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A Rare Case Report of Crigler Najjar Syndrome Type II.

Cureus 2021 Jan 12;13(1):e12669. Epub 2021 Jan 12.

Internal Medicine, Services Institute of Medical Sciences, Lahore, PAK.

Crigler-Najjar syndrome is an inborn error of metabolism caused by a point mutation in one of the five exons of UGT1A1 gene, the product of which is responsible for elimination of bilirubin via bile. A number of hyperbilirubinemia disorders similar to Crigler-Najjar syndrome are reported, but they differ in their level of unconjugated bilirubin and responses to the treatment. Here we report a 14-year-old male patient admitted to hospital with the complaint of vomiting and frequent tonsillitis. Read More

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January 2021

Outcome of liver transplantation and prevalence of liver fibrosis in Crigler-Najjar syndrome.

Clin Transplant 2021 Apr 22;35(4):e14219. Epub 2021 Feb 22.

Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Crigler-Najjar syndrome (CNS) is a rare inherited disorder that is characterized by high levels of non-hemolytic, unconjugated hyperbilirubinemia leading to brain damage and even death. Liver transplantation (LT) can correct the metabolic defect, but there are little data regarding LT in this patient cohort. The liver parenchyma has been considered to be structurally normal in CNS, but there is growing evidence of clinically silent but histologically significant fibrosis in CNS patients. Read More

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Efficacy of AAV8-h with Rapamycin in neonatal, suckling, and juvenile rats to model treatment in pediatric CNs patients.

Mol Ther Methods Clin Dev 2021 Mar 3;20:287-297. Epub 2020 Dec 3.

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

A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 (h) to treat inherited severe unconjugated hyperbilirubinemia (Crigler-Najjar syndrome) is ongoing, but preclinical data suggest that long-term efficacy in children is impaired due to loss of transgene expression upon hepatocyte proliferation in a growing liver. This study aims to determine at what age long-term efficacy can be obtained in the relevant animal model and whether immune modulation allows re-treatment using the same AAV vector. Neonatal, suckling, and juvenile Ugt1a1-deficient rats received a clinically relevant dose of AAV8-h, and serum bilirubin levels and anti-AAV8 neutralizing antibodies (NAbs) in serum were monitored. Read More

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Generation of a Crigler-Najjar Syndrome Type I patient-derived induced pluripotent stem cell line CNS705 (HHUUKDi005-A).

Stem Cell Res 2021 03 12;51:102167. Epub 2021 Jan 12.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address:

Human fibroblasts cells from a Crigler-Najjar Syndrome (CNS) patient were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids expressing OCT4, SOX2, NANOG, KLF4, c-MYC and LIN28. The derived CNS705-iPSC line is homozygous for the UGT1A1 c.877_890delTACATTAATGCTTCinsA mutation. Read More

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Novel mutations in Uridyl-diphosphate-glucuronosyl-transferase 1A1 (UGT1A1) gene in Tunisian patients with unconjugated hyperbilirubinemia.

Eur J Med Genet 2021 Feb 7;64(2):104139. Epub 2021 Jan 7.

Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire, Tunisie.

Introduction: Unconjugated hyperbilirubinemia (UCB) is a feature of Gilbert's syndrome (GS) and Crigler-Najjar's syndrome (CNS), which are two hereditary defects in bilirubin metabolism. Both syndromes are linked to mutations in the UGT1A1 gene, which cause either the decrease or the absence of the UGT1A1 enzymatic activity. Here, we investigated the molecular basis of the UGT1A1 gene in Tunisian patients presenting with unconjugated hyperbilirubinemia. Read More

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February 2021

Combined Spinal and TAP Blocks for Laparoscopic Cholecystectomy for a Patient with Crigler-Najjar Type 2: A Case Report.

Niger J Clin Pract 2020 Dec;23(12):1772-1775

Department of Anesthesiology, University of Health Sciences, Gazi Yasargil Diyarbakir Training and Research Hospital, Diyarbakir, Turkey.

Crigler-Najjar syndrome is a rare disease which is associated with congenital deficiency of uridine-diphosphate-gulukronyltransferase (UDP-glucuronosyltransferase, UGT) enzyme. In the surgery of these patients, it is necessary to use an anesthetic method that causes less damage to the liver. Spinal anesthesia is a good alternative to general anesthesia in these patients. Read More

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December 2020

Effects of Different Cold Preservation Solutions on the Functions of Cultured Isolated Human Hepatocytes.

Int J Organ Transplant Med 2020 ;11(1):15-25

Transplant Research Center, Shiraz University of Medical Sciences.

Background: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and study of drug toxicity.

Objective: To determine which cold preservation solution is better maintain the liver function. Read More

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January 2020

p.Cys223Tyr mutation causing Crigler-Najjar syndrome type II.

JGH Open 2020 Oct 16;4(5):1009-1011. Epub 2020 May 16.

Department of Liver Disease, The Second Hospital of Nanjing Nanjing University of Chinese Medicine Nanjing China.

Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically diagnosed with Crigler-Najjar Syndrome types II (CNs-II) can be clinically diagnosed which were based on the level of total bilirubin, efficacy of phenobarbital treatment, normal liver architecture and exclusion of hemolysis. Diagnosis was also confirmed by UGT1A1 gene mutations, which by sequencing the coding region for UGT1A1 gene mutations, which were the homozygous mutations c. Read More

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October 2020

Successful living donor liver transplantation plus domino-auxiliary partial orthotopic liver transplantation for pediatric patients with metabolic disorders.

Pediatr Surg Int 2020 Dec 10;36(12):1443-1450. Epub 2020 Oct 10.

Organ Transplantation Center, Tianjin First Central Hospital, No.24 Fukang Road, Nankai District, 300192, Tianjin, China.

Purpose: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders.

Methods: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. Read More

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December 2020

Oral findings in Crigler-Najjar syndrome type I.

Spec Care Dentist 2020 Nov 3;40(6):611-612. Epub 2020 Sep 3.

Oral Medicine and Special Care Dentistry, School of Dentistry, The University of Jordan, Amman, Jordan.

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November 2020

A Quantitative Potency Assay for Adeno-Associated Virus Vectors Encoding for the Transgene.

Mol Ther Methods Clin Dev 2020 Sep 3;18:250-258. Epub 2020 Jun 3.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, AG&M, 1105 BK Amsterdam, the Netherlands.

Potency assessment of clinical-grade vector lots is crucial to support adeno-associated virus (AAV) vector release and is required for future marketing authorization. We have developed and validated a cell-based, quantitative potency assay that detects both transgenic expression and activity of an AAV8-h vector, which is currently under clinical evaluation for the treatment of Crigler-Najjar syndrome. Potency of AAV8-h was evaluated . Read More

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September 2020

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

Pediatr Res 2021 Feb 1;89(3):510-517. 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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February 2021

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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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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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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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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February 2020

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

Sci Rep 2020 01 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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January 2020

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

Hepatology 2020 06 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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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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October 2019

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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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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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 01 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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January 2020

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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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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September 2019