Crigler-Najjar Syndrome

A familial form of congenital hyperbilirubinemia transmitted as an autosomal recessive trait. It is characterized by icterus and brain damage caused by a glucuronyl transferase deficiency in the liver and faulty bilirubin conjugation.

Also Known As:

Crigler Najjar Syndrome; Crigler Najjar Syndrome, Type 1; Crigler-Najar Syndrome; Crigler-Najjar Syndrome, Type I; Familial Nonhemolytic Unconjugated Hyperbilirubinemia; Hereditary Unconjugated Hyperbilirubinemia; Crigler Najar Syndrome; Crigler Najjar Syndrome, Type I; Crigler Najjar Syndromes; Hereditary Unconjugated Hyperbilirubinemias; Hyperbilirubinemia, Hereditary Unconjugated; Najjar Syndrome, Crigler; Syndrome, Crigler Najjar; Unconjugated Hyperbilirubinemia, Hereditary

Networked: 246 relevant articles (11 outcomes, 12 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hyperbilirubinemia
2.	Gilbert Disease
3.	Ornithine Carbamoyltransferase Deficiency Disease
4.	Propionic Acidemia
5.	progressive familial intrahepatic 1 Cholestasis

Experts

1.	Bosma, Piter J: 5 articles (03/2021 - 01/2010)
2.	Dhawan, Anil: 5 articles (04/2020 - 04/2006)
3.	Maruo, Yoshihiro: 5 articles (02/2016 - 01/2002)
4.	Sato, Hiroshi: 5 articles (02/2016 - 01/2002)
5.	Roy-Chowdhury, Jayanta: 4 articles (01/2019 - 09/2009)
6.	Roy-Chowdhury, Namita: 4 articles (01/2019 - 09/2009)
7.	Costa, Elísio: 4 articles (12/2015 - 01/2006)
8.	Fox, Ira J: 4 articles (07/2015 - 06/2003)
9.	Brunetti-Pierri, Nicola: 4 articles (06/2014 - 04/2011)
10.	Lee, S W: 4 articles (02/2003 - 11/2001)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Crigler-Najjar Syndrome:

1.	BilirubinIBA 09/21/2018 - "Based on a significant reduction in serum total bilirubin levels, we determined the minimally effective dose in this mouse model of Crigler-Najjar syndrome to be 2.5 × 1011 GC/kg." 02/15/1986 - "The method was helpful in diagnosing biliary-tract obstruction in a newborn and a partial deficiency state of bilirubin conjugation (Crigler-Najjar syndrome) in a 10-year-old male. " 04/01/1997 - "The Gunn rat is an excellent model of Crigler-Najjar syndrome, type 1. In previous studies we demonstrated that heterotopic 15-20-cm jejunal transplants from Wistar rats lowered serum bilirubin levels by 40%, and the reduction was transient (6 weeks). " 02/13/2023 - "Analysis of the local conformation of ACE in plasma of patients with Gilbert and Crigler-Najjar syndromes allowed us to speculate that binding of mAbs 1G12 and 6A12 to plasma ACE could be a natural sensor for estimation of free bilirubin level in plasma. " 10/01/2017 - "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. "
2.	Uridine Diphosphate (UDP)IBA 12/15/2018 - "Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. " 12/01/2005 - "There is considerable evidence suggesting that genetic damages to human uridine diphosphate glucuronyltransferase (UDPGT) gene located on clhromosome 2q37 are responsible for hereditary unconjugated hyperbilirubinemias (HUHB). " 04/01/1990 - "Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I." 03/12/2021 - "A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 (hUGT1A1) 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. " 05/20/2020 - "Objective: 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. "
3.	Glucuronosyltransferase (UDP Glucuronosyltransferase)IBA 01/01/2019 - "The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. " 01/01/2019 - "The Gunn rat, a Crigler-Najjar syndrome model animal lacking UDP-glucuronosyltransferase (UGT1A1), was used as recipient. " 05/01/2009 - "Identification of a novel deletion in UDP-glucuronosyltransferase gene in a patient with Crigler-Najjar syndrome type I." 01/01/2006 - "Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes." 02/01/2003 - "To test this hypothesis, congeneic normal rat hepatocytes were transplanted into UDP-glucuronosyltransferase (UGT1A1)-deficient jaundiced Gunn rats (a model of Crigler-Najjar syndrome type I), following HIR and adenovirus-mediated FasL gene transfer. "
4.	bilirubin glucuronoside glucuronosyltransferaseIBA 09/01/2012 - "Analysis of bilirubin UDP-glucuronosyltransferase gene mutations in an unusual Crigler-Najjar syndrome patient." 09/27/2006 - "Here, we evaluated the SLIT approach in Gunn rats, the animal model for Crigler-Najjar syndrome type 1, a defect in bilirubin UDP-glucuronosyltransferase (BUGT). " 01/01/2006 - "Hematologically important mutations: bilirubin UDP-glucuronosyltransferase gene mutations in Gilbert and Crigler-Najjar syndromes." 11/01/2003 - "We analyzed the bilirubin UDP-glucuronosyltransferase gene in a female Chinese patient with Crigler-Najjar syndrome type I. Relatives of the patient were also analyzed. " 11/01/2003 - "A novel missense mutation of the bilirubin UDP-glucuronosyltransferase gene in a Turkish patient with Crigler-Najjar syndrome type 1."
5.	UGT1A1 enzymeIBA 01/01/2020 - "CORRIGENDUM: Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1." 01/01/2018 - "Quantitative Systems Pharmacology Model of hUGT1A1-modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler-Najjar Syndrome Type 1." 04/01/2013 - "Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database." 08/22/2023 - "Crigler-Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler-Najjar Syndrome. " 01/01/2016 - "Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. "
6.	Phenobarbital (Luminal)FDA Link 08/01/2016 - "[Phenobarbital in Crigler-Najjar syndrome type 1: A therapeutic option]." 02/01/2014 - "Crigler-Najjar syndrome (CNS) is described as severe infantile, nonhemolytic, unconjugated hyperbilirubinemia and is divided into type I and type II according to the patient's response to phenobarbital treatment. " 06/01/1996 - "The combination of phenobarbital treatment and orthotopic small bowel transplantation may be an appropriate therapeutic alternative to liver transplantation in the management of Crigler-Najjar syndrome, type 1." 10/01/2020 - "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. " 10/03/2018 - "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. "
7.	RNA (Ribonucleic Acid)IBA 11/01/2023 - "The primary diseases included Niemann-Pick disease, propionic acidemia, decompensated cirrhosis, biliary atresia, and Crigler-Najjar syndrome type I. All of the patients were onset with fever before or when getting RNA-positive results at the age of 3 (Range: 1-13) years. " 05/01/1992 - "RNA blot showed that the two bilirubin-UDP-glucuronosyltransferase messenger RNAs in the liver of the Crigler-Najjar syndrome, type I patient were of normal length but were reduced in concentration.(ABSTRACT TRUNCATED AT 250 WORDS)"
8.	calcium phosphateIBA 02/01/1997 - "Calcium phosphate binds unconjugated bilirubin in vitro, and dietary calcium phosphate supplementation reduces the serum bilirubin level in rats with hereditary unconjugated hyperbilirubinemia (Gunn rats). " 12/01/2011 - "In type 1 Crigler-Najjar syndrome, extensive phototherapy is the mainstay of treatment, in association with adjuvant therapy to bind photobilirubin such as calcium phosphate, cholestyramine, or agar, until liver transplantation can be carried out. "
9.	Polycyclic Aromatic Hydrocarbons (Polynuclear Aromatic Hydrocarbons)IBA 10/01/1992 - "Genetic deficiencies in bilirubin UDP-glucuronosyltransferase (GT) occur in >5% of the population (Gilbert's disease, Crigler-Najjar syndromes), and this could predispose such people to the toxic effects of polycyclic aromatic hydrocarbons and other environmental chemicals that are eliminated substantially by glucuronidation. "
10.	Factor VII (Proconvertin)IBA 01/01/2008 - "We reviewed the explant livers of seven children with metabolic disorders [ornithine-transcarbamylase deficiency (one), coagulation factor VII deficiency (three), Crigler-Najjar syndrome (one), progressive familial intrahepatic cholestasis type 2 (PFIC-2) deficiency (two)] who received allograft hepatocytes by intraportal infusion with improvement in phenotype, although all later underwent liver transplantation (LT). "

Therapies and Procedures

1.	Liver Transplantation 05/01/2013 - "In this study, we describe two siblings who were diagnosed with Crigler-Najjar syndrome type I who underwent a successful liver transplantation using a single cadaveric organ, together with their neurophysiological follow-up and review of the literature. " 07/01/2023 - "Liver Transplantation in a Child With Crigler-Najjar Syndrome Type I: A Case Report With Review of the Literature." 01/01/2020 - "For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. " 06/01/2014 - "This method of delivery could thereby be a safer alternative to liver transplantation for long-term treatment of Crigler-Najjar syndrome type I." 10/01/2012 - "Crigler-Najjar syndrome type I (CNS I) is a very rare autosomal recessive inherited disease that liver transplantation can properly deal with. "
2.	Phototherapy (Light Therapy) 01/01/2014 - "After transient response to phototherapy, the patient was referred to a tertiary medical center in which an extensive work up ruled out other etiologies and the diagnosis of type I Crigler-Najjar syndrome was established. " 11/01/1996 - "Patients with Crigler-Najjar syndrome Type I are being treated with long-term blue-light phototherapy into childhood, adolescence and beyond. " 11/01/1996 - "Improvements in long term phototherapy for patients with Crigler-Najjar syndrome type I." 10/01/1988 - "Crigler-Najjar syndrome: treatment at home with phototherapy." 06/01/1983 - "Long term phototherapy in Crigler-Najjar syndrome."
3.	Intravenous Infusions 08/17/2023 - "We report the results of the dose-escalation portion of a phase 1-2 study evaluating the safety and efficacy of a single intravenous infusion of an adeno-associated virus serotype 8 vector encoding UGT1A1 in patients with the Crigler-Najjar syndrome that was being treated with phototherapy. "
4.	Therapeutics 08/01/1996 - "Current therapy for Crigler-Najjar syndrome type 1: report of a world registry." 05/01/1975 - "[Diagnosis and therapy of the Crigler-Najjar syndrome]." 01/01/2017 - "Gunn Rats as a Surrogate Model for Evaluation of Hepatocyte Transplantation-Based Therapies of Crigler-Najjar Syndrome Type 1." 06/01/2015 - "We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy." 01/01/2021 - "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). "
5.	Injections 10/01/2013 - "In conclusion, ultrasound-guided percutaneous injection of HDAd vectors into liver parenchyma resulted in improved hepatocyte transduction and reduced toxicity compared with systemic injections and is clinically attractive for liver-directed gene therapy of Crigler-Najjar syndrome."